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1
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Khandelwal R, Vasava M, Abhirami RB, Karsharma M. Recent advances in triazole synthesis via click chemistry and their pharmacological applications: A review. Bioorg Med Chem Lett 2024; 112:129927. [PMID: 39153663 DOI: 10.1016/j.bmcl.2024.129927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 08/19/2024]
Abstract
Click chemistry is a flexible method featuring only the most feasible and efficient chemical reactions. The synthesis of 1,2,3-triazole from azides and terminal acetylenes using copper(I) as a catalyst is an extremely powerful reaction due to the extreme dependability, good selectivity, and biocompatibility of the starting materials. Triazole molecules are more than simple passive linkers; through hydrogen bonding and dipole interactions, they rapidly bind with biological targets. Its applications in drug development are expanding, ranging from target-oriented in situ chemistry and combinatorial mechanisms for lead generation to bioconjugation methods to study proteins and DNA. The click chemistry has frequently been used to speed up drug discovery and optimization processes in the past few years. The click chemistry reaction based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a biochemical process with applications in medicinal chemistry and chemical biology. Thus, click reactions are an essential component of the toolkit for medicinal chemistry and help medicinal chemists overcome the barriers in chemical reactions, increase throughput, and improve the standards of compound libraries. The review highlights the recent advancements in the copper-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry approach for synthesizing biologically important triazole moieties with a greater emphasis on synthesis methodologies and pharmacological applications. Additionally, the triazole-based FDA-approved drugs are also discussed with their mode of action to highlight the importance of the click chemistry approach in synthesizing the bioactive triazole compounds.
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Affiliation(s)
- Riya Khandelwal
- School of Pharmacy, National Forensic Sciences University, Gandhinagar, Gujarat, India
| | - Mahesh Vasava
- School of Pharmacy, National Forensic Sciences University, Gandhinagar, Gujarat, India.
| | - R B Abhirami
- School of Pharmacy, National Forensic Sciences University, Gandhinagar, Gujarat, India
| | - Manaswini Karsharma
- School of Pharmacy, National Forensic Sciences University, Gandhinagar, Gujarat, India
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2
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Farghaly TA, Masaret GS, Riyadh SM, Harras MF. A Literature Review Focusing on the Antiviral Activity of [1,2,4] and [1,2,3]-triazoles. Mini Rev Med Chem 2024; 24:1602-1629. [PMID: 38008942 DOI: 10.2174/0113895575277122231108095511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 09/07/2023] [Accepted: 09/09/2023] [Indexed: 11/28/2023]
Abstract
Out of a variety of heterocycles, triazole scaffolds have been shown to play a significant part in a wide array of biological functions. Many drug compounds containing a triazole moiety with important antimicrobial, anticancer and antidepressant properties have been commercialized. In addition, the triazole scaffold exhibits remarkable antiviral activity either incorporated into nucleoside analogs or non-nucleosides. Many synthetic techniques have been produced by scientists around the world as a result of their wide-ranging biological function. In this review, we have tried to summarize new synthetic methods produced by diverse research groups as well as provide a comprehensive description of the function of [1,2,4] and [1,2,3]-triazole derivatives as antiviral agents. Antiviral triazole compounds have been shown to target a wide variety of molecular proteins. In addition, several strains of viruses, including the human immunodeficiency virus, SARS virus, hepatitis B and C viruses, influenza virus, Hantavirus, and herpes virus, were discovered to be susceptible to triazole derivatives. This review article covered the reports for antiviral activity of both 1,2,3- and 1,2,4-triazole moieties up to 2022.
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Affiliation(s)
- Thoraya A Farghaly
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, 21514, Saudi Arabia
| | - Ghada S Masaret
- Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah Almukaramah, 21514, Saudi Arabia
| | - Sayed M Riyadh
- Chemistry Department, Faculty of Science, University of Cairo, Giza 12613, Egypt
| | - Marwa F Harras
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
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3
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Mao L, Wang S, Qu Y, Wang H, Zhao Y, Zhu C, Zhang Z, Jin C, Herdewijn P, Liu FW, Wang Z. Design, synthesis, and anti-respiratory syncytial virus potential of novel 3-(1,2,3-triazol-1-yl)furoxazine-fused benzimidazole derivatives. Eur J Med Chem 2023; 261:115799. [PMID: 37722289 DOI: 10.1016/j.ejmech.2023.115799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2023] [Revised: 08/29/2023] [Accepted: 09/06/2023] [Indexed: 09/20/2023]
Abstract
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in infants, children, and older persons. Currently, the only approved anti-viral chemotherapeutic drug for RSV treatment is ribavirin aerosol; however, its significant toxicity has led to restricted clinical use. In a previous study, we developed various benzimidazole derivatives against RSV. In this study, we synthesised 3-azide substituted furoxazine-fused benzimidazole derivatives by sulfonylation and azide substitution of the 3-hydroxyl group of the furoxazine-fused benzimidazole derivatives. Subsequently, a series of 3-(1,2,3-triazol-1-yl)-substituted furoxazine-fused benzimidazole derivatives were synthesised using the classical click reaction. Biological evaluations of the target compounds indicated that compound 4a-2 had higher activity against RSV (EC50 = 12.17 μM) and lower cytotoxicity (CC50 = 390.64 μM). Compound 4a-2 exerted anti-viral effects against the RSV Long strain by inhibiting apoptosis and the elevation of reactive oxygen species (ROS) and inflammatory factors caused by viral infection in vitro. Additionally, the clinical symptoms of the virus-infected mice were markedly relieved, and the viral load in the lung tissues was dramatically decreased. The biosafety profile of compound 4a-2 was also favourable, showing no detectable adverse effects on any of the major organs in vivo. These findings underscore the potential of compound 4a-2 as a valuable therapeutic option for combating RSV infections while also laying the foundation for further research and development in the field.
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Affiliation(s)
- Lu Mao
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Anti-viral Medicines Research and Development, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Song Wang
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China
| | - Ying Qu
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Anti-viral Medicines Research and Development, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Haixia Wang
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China
| | - Yifan Zhao
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China
| | - Chuantao Zhu
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China
| | - Zhongmou Zhang
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Anti-viral Medicines Research and Development, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China
| | - Chengyun Jin
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | - Piet Herdewijn
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; Medicinal Chemistry, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
| | - Feng-Wu Liu
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China.
| | - Zhenya Wang
- XNA Platform, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; Key Laboratory of "Runliang" Anti-viral Medicines Research and Development, Institute of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; International Joint Research Centre of National Animal Immunology, College of Veterinary Medicine, Henan Agricultural University, Zhengdong New District Longzi Lake 15#, Zhengzhou 450046, China.
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4
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Jurado S, Illa O, Álvarez-Larena A, Pannecouque C, Busqué F, Alibés R. Conformationally Locked Carbocyclic Nucleosides Built on a 4'-Hydroxymethyl-3'-hydroxybicyclo[4.1.0]heptane Template. Stereoselective Synthesis and Antiviral Activity. J Org Chem 2022; 87:15166-15177. [PMID: 36300902 PMCID: PMC9680032 DOI: 10.1021/acs.joc.2c01661] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Two new families of enantiomerically pure carbocyclic nucleoside analogues based on a cyclohexane moiety with five chiral centers and a fused cyclopropyl ring have been synthesized. A highly regio- and stereoselective synthetic approach for the modular construction of the functionalized bicyclo[4.1.0]heptyl azide intermediate 6 has been established. Key steps to achieve this asymmetric synthesis involved highly diastereoselective allylic oxidation and hydroboration reactions. The first family of compounds, 1a,b and 2, presents different natural nucleobases, whereas the second one 3a-e bears functionalized 1,2,3-triazoles. These derivatives have been tested as antiviral agents, and compound 3d has shown to display moderate activity against coxsackie B4 virus.
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Affiliation(s)
- Sergio Jurado
- Departament
de Química, Universitat Autònoma
de Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Ona Illa
- Departament
de Química, Universitat Autònoma
de Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Angel Álvarez-Larena
- Servei
de Difracció de Raigs X, Universitat
Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain
| | - Christophe Pannecouque
- Department
of Microbiology and Immunology, Laboratory of Virology and Chemotherapy,
Rega Institute for Medical Research, KU
Leuven, Herestraat 49, Leuven B-3000, Belgium
| | - Félix Busqué
- Departament
de Química, Universitat Autònoma
de Barcelona, Bellaterra, Barcelona 08193, Spain,
| | - Ramon Alibés
- Departament
de Química, Universitat Autònoma
de Barcelona, Bellaterra, Barcelona 08193, Spain,
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5
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Kumar R, Maity J, Mathur D, Verma A, Rana N, Kumar M, Kumar S, Prasad AK. Green synthesis of triazolo-nucleoside conjugates via azide–alkyne C–N bond formation. PHYSICAL SCIENCES REVIEWS 2022. [DOI: 10.1515/psr-2021-0090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Modified nucleosides are the core precursors for the synthesis of artificial nucleic acids, and are important in the field of synthetic and medicinal chemistry. In order to synthesize various triazolo-compounds, copper and ruthenium catalysed azide–alkyne 1,3-dipolar cycloaddition reactions also known as click reaction have emerged as a facile and efficient tool due to its simplicity and convenient conditions. Introduction of a triazole ring in nucleosides enhances their therapeutic value and various photophysical properties. This review primarily focuses on the plethora of synthetic methodologies being employed to synthesize sugar modified triazolyl nucleosides, their therapeutic importance and various other applications.
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Affiliation(s)
- Rajesh Kumar
- Department of Chemistry , R.D.S. College, B.R.A. Bihar University , Muzaffarpur , India
| | - Jyotirmoy Maity
- Department of Chemistry , St. Stephen’s College, University of Delhi , Delhi , India
| | - Divya Mathur
- Department of Chemistry , Daulat Ram College, University of Delhi , Delhi , India
| | - Abhishek Verma
- Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India
| | - Neha Rana
- Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India
| | - Manish Kumar
- Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India
| | - Sandeep Kumar
- Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India
| | - Ashok K. Prasad
- Department of Chemistry , Bioorganic Laboratory, University of Delhi , Delhi , India
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6
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Shen GH, Hong JH. Chemical Synthesis of Acyclic Nucleoside Phosphonate Analogs Linked with Cyclic Systems between the Phosphonate and the Base Moieties. Curr Med Chem 2020; 27:5918-5948. [DOI: 10.2174/0929867326666190620100217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 03/11/2019] [Accepted: 03/15/2019] [Indexed: 11/22/2022]
Abstract
The syntheses of acyclic nucleoside phosphonate (ANP) analogs linked with cyclic systems
are described in the present review. The purpose of the review is to report the methodology of
ANP analogs and to give an idea on the synthesis of a therapeutic structural feature of such analogs.
The cyclopropane systems were mainly prepared by diazomethane cyclopropanation catalyzed by
Pd(OAc)2, intramolecular alkylation, Kulinkovich cyclopropanation, and use of difluorocyclopropane,
and so forth. The preparation of methylenecyclopropane system was made by diazoacetate
cyclopropanation catalyzed by Rhodium followed by addition-elimination reactions. For the preparation
of a variety of tethered 1,2,3-triazole systems, 1,3-dipolar cycloaddition between azidealkylphosphonates
and propargylated nucleobases was mainly applied. The formation of various
phosphonate moieties was achieved via phosphonylation of alkoxide, cross-coupling between
BrZnCF2P (O)(OEt)2 with iodoalkens catalyzed by CuBr, Michaelis-Arbuzov reaction with phosphite,
and Rh(II)-catalyzed O-H insertion, and so forth.
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Affiliation(s)
- Guang Huan Shen
- Heilongjiang Provincial Key Laboratory of Drug Prevention and Treatment for Senile Diseases, College of Pharmacy, Harbin University of Commerce, Harbin 150076, China
| | - Joon Hee Hong
- College of Pharmacy, Chosun University, Kwangju 501-759, Korea
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7
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Hartwich A, Zdzienicka N, Schols D, Andrei G, Snoeck R, Głowacka IE. Design, synthesis and antiviral evaluation of novel acyclic phosphonate nucleotide analogs with triazolo[4,5- b]pyridine, imidazo[4,5- b]pyridine and imidazo[4,5- b]pyridin-2(3 H)-one systems. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2019; 39:542-591. [PMID: 31550993 DOI: 10.1080/15257770.2019.1669046] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
A new series of phosphonylated triazolo[4,5-b]pyridine (1-deaza-8-azapurine), imidazo[4,5-b]pyridine (1-deazapurine) and imidazo[4,5-b]pyridin-2(3H)-one (1-deazapurin-8-one) were synthesized from 2-chloro-3-nitropyridine and selected diethyl ɷ-aminoalkylphosphonates followed by reduction of the nitro group and cyclization. In the final step O,O-diethylphosphonates were transformed into the corresponding phosphonic acids. All synthesized compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses and their cytotoxic potencies were also established. Compound 12f showed marginal activity against cytomegalovirus Davis strain (EC50 = 76.47 μM) in human embryonic lung (HEL) cells while compounds 10g (EC50 = 52.53 μM) and 12l (EC50 = 61.70 μM) were minimally active against the varicella-zoster virus Oka strain in HEL cells. Compounds under investigation were not cytotoxic at the maximum concentration evaluated (100 µM).
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Affiliation(s)
- Anna Hartwich
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland
| | - Nee Zdzienicka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland
| | | | - Graciela Andrei
- Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Robert Snoeck
- Rega Institute for Medical Research, KU Leuven, Leuven, Belgium
| | - Iwona E Głowacka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland
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8
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Ruddarraju RR, Murugulla AC, Kotla R, Tirumalasetty MCB, Wudayagiri R, Donthabakthuni S, Maroju R. Design, synthesis, anticancer activity and docking studies of theophylline containing 1,2,3-triazoles with variant amide derivatives. MEDCHEMCOMM 2017; 8:176-183. [PMID: 30108703 PMCID: PMC6072493 DOI: 10.1039/c6md00479b] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Accepted: 10/18/2016] [Indexed: 11/21/2022]
Abstract
A new series of theophylline analogues containing 1,2,3-triazoles with different amide groups (22-41) has been designed and synthesized, and their biological activities have been evaluated as potential anticancer agents. The anticancer activities of the synthesized compounds were studied in four cancer cell lines viz. lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375). Furthermore, these compounds were screened for computational ADME and Lipinski's analysis followed by molecular docking and binding energy calculations against the various therapeutic targets involved in cell proliferation. The in vitro results demonstrate that compounds 22, 27, 36 and 40 have pivotal anticancer activity. Among these, compounds 22 and 27 have significant cytotoxic activity in all three cell lines; the in silico docking studies also reveal that compounds 22, 27 and 36 have good dock scores, binding affinities and binding energies towards human epidermal growth factor receptor 2. This is the first report to demonstrate theophylline hybrids containing 1,2,3-triazoles as potential anticancer agents.
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Affiliation(s)
- Radhakrishnam Raju Ruddarraju
- Dr.MACS Bio-Pharma Pvt. Ltd , Factory: Plot-79/B&C , Pasamylaram , Medak (Dist)-502307 , Patancheru , Telangana , India .
| | - Adharvana Chari Murugulla
- Dr.MACS Bio-Pharma Pvt. Ltd , Factory: Plot-79/B&C , Pasamylaram , Medak (Dist)-502307 , Patancheru , Telangana , India .
| | - Ravindar Kotla
- Dr.MACS Bio-Pharma Pvt. Ltd , Factory: Plot-79/B&C , Pasamylaram , Medak (Dist)-502307 , Patancheru , Telangana , India .
| | - Muni Chandra Babu Tirumalasetty
- Bioinformatics Center , Division of Molecular Biology , Department of Zoology , Sri Venkateswara University , Tirupati-517 502 , Andhra Pradesh , India
| | - Rajendra Wudayagiri
- Bioinformatics Center , Division of Molecular Biology , Department of Zoology , Sri Venkateswara University , Tirupati-517 502 , Andhra Pradesh , India
| | - Shobha Donthabakthuni
- Dr.MACS Bio-Pharma Pvt. Ltd , Factory: Plot-79/B&C , Pasamylaram , Medak (Dist)-502307 , Patancheru , Telangana , India .
| | - Ravichandar Maroju
- Mahatma Gandhi Institute of Technology , Gandipet , Hyderabad-500 075 , Telangana , India
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9
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González-Calderón D, Mejía-Dionicio MG, Morales-Reza MA, Aguirre-de Paz JG, Ramírez-Villalva A, Morales-Rodríguez M, Fuentes-Benítes A, González-Romero C. Antifungal activity of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides: A novel type of compound afforded by azide-enolate (3+2) cycloaddition. Bioorg Chem 2016; 69:1-6. [PMID: 27656774 DOI: 10.1016/j.bioorg.2016.09.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 09/01/2016] [Accepted: 09/14/2016] [Indexed: 01/06/2023]
Abstract
The first report of 1'-homo-N-1,2,3-triazol-bicyclic carbonucleosides (7a and 7b) is described herein. Azide-enolate (3+2) cycloaddition afforded the synthesis of this novel type of compound. Antifungal activity was evaluated in vitro against four filamentous fungi (Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis) as well as nine species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 7a and 7b are promising candidates for complementary biological studies due to their good activity against Candida spp.
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Affiliation(s)
- Davir González-Calderón
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico.
| | - María G Mejía-Dionicio
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - Marco A Morales-Reza
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - José G Aguirre-de Paz
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - Alejandra Ramírez-Villalva
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - Macario Morales-Rodríguez
- Departamento de Microbiología, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - Aydeé Fuentes-Benítes
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico
| | - Carlos González-Romero
- Departamento de Química Orgánica, Facultad de Química, Universidad Autónoma del Estado de México, Paseo Colón/Paseo Tollocan s/n, Toluca, Estado de México 50120, Mexico.
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10
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Ouahrouch A, Taourirte M, Schols D, Snoeck R, Andrei G, Engels JW, Lazrek HB. Design, Synthesis, and Antiviral Activity of Novel Ribonucleosides of 1,2,3-Triazolylbenzyl-aminophosphonates. Arch Pharm (Weinheim) 2016; 349:30-41. [PMID: 26575425 PMCID: PMC4832832 DOI: 10.1002/ardp.201500292] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Revised: 10/09/2015] [Accepted: 10/14/2015] [Indexed: 01/13/2023]
Abstract
A novel series of ribonucleosides of 1,2,3-triazolylbenzyl-aminophosphonates was synthesized through the Kabachnik-Fields reaction using I2 as catalyst followed by copper-catalyzed cycloaddition of the azide-alkyne reaction (CuAAC). All structures of the newly prepared compounds were characterized by (1) H NMR, (13) C NMR, and HRMS spectra. The structures of 2e, 2f, 3d, and 3g were further confirmed by X-ray diffraction analysis. These compounds were tested against various strains of DNA and RNA viruses; compounds 4b and 4c showed a modest inhibitory activity against respiratory syncytial virus (RSV) and compound 4h displayed modest inhibitory activity against Coxsackie virus B4.
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Affiliation(s)
- Abdelaaziz Ouahrouch
- Department of Chemistry, Faculty of Sciences and Technology Gueliz (FSTG)Laboratory of Bioorganic and Macromolecular ChemistryMarrakeshMorocco
- Department of Chemistry, Faculty of Sciences SemlaliaLaboratory of Biomolecular and Medicinal ChemistryMarrakeshMorocco
- Institute for Organic Chemistry and Chemical BiologyGoethe‐University Frankfurt am MainFrankfurt am MainGermany
| | - Moha Taourirte
- Department of Chemistry, Faculty of Sciences and Technology Gueliz (FSTG)Laboratory of Bioorganic and Macromolecular ChemistryMarrakeshMorocco
| | | | - Robert Snoeck
- Rega Institute for Medical ResearchKU LeuvenLeuvenBelgium
| | | | - Joachim W. Engels
- Institute for Organic Chemistry and Chemical BiologyGoethe‐University Frankfurt am MainFrankfurt am MainGermany
| | - Hassan B. Lazrek
- Department of Chemistry, Faculty of Sciences SemlaliaLaboratory of Biomolecular and Medicinal ChemistryMarrakeshMorocco
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11
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Bioactive nucleoside analogues possessing selected five-membered azaheterocyclic bases. Eur J Med Chem 2015; 97:409-18. [DOI: 10.1016/j.ejmech.2014.11.057] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 11/25/2014] [Accepted: 11/27/2014] [Indexed: 11/23/2022]
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12
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Green One-Pot Solvent-Free Synthesis of Pyrazolo[1,5-a]pyrimidines, Azolo[3,4-d]pyridiazines, and Thieno[2,3-b]pyridines Containing Triazole Moiety. J Heterocycl Chem 2015. [DOI: 10.1002/jhet.2343] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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13
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Tran TTT, Ngo NT, Dinh TH, Vo-Thanh G, Legoupy S. Synthesis of Novel Triazolo Cyclobutane Nucleoside Analogs. B KOREAN CHEM SOC 2015. [DOI: 10.1002/bkcs.10270] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Thi Thu Thuy Tran
- Institute of Natural Products Chemistry; Vietnam Academy of Science and Technology; Hanoi Vietnam
| | - Ngoc Thang Ngo
- Institute of Natural Products Chemistry; Vietnam Academy of Science and Technology; Hanoi Vietnam
| | - Thi Ha Dinh
- Institute of Natural Products Chemistry; Vietnam Academy of Science and Technology; Hanoi Vietnam
| | - Giang Vo-Thanh
- Equipe de Catalyse Moléculaire-ICMMO; Bât 420 Université Paris-Sud 11; 91405 Orsay Cedex France
| | - Stéphanie Legoupy
- LUNAM Université; Université d'Angers, CNRS UMR 6200, Laboratoire MOLTECH-Anjou; 49045 ANGERS cedex France
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14
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Hassan S, Müller TJJ. Multicomponent Syntheses based upon Copper-Catalyzed Alkyne-Azide Cycloaddition. Adv Synth Catal 2015. [DOI: 10.1002/adsc.201400904] [Citation(s) in RCA: 124] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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15
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A click chemistry approach to the synthesis of 3′-deoxy-2′-substituted carbanucleoside precursors. Tetrahedron 2015. [DOI: 10.1016/j.tet.2014.11.043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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16
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Głowacka IE, Balzarini J, Andrei G, Snoeck R, Schols D, Piotrowska DG. Design, synthesis, antiviral and cytostatic activity of ω-(1H-1,2,3-triazol-1-yl)(polyhydroxy)alkylphosphonates as acyclic nucleotide analogues. Bioorg Med Chem 2014; 22:3629-41. [PMID: 24906510 PMCID: PMC7127666 DOI: 10.1016/j.bmc.2014.05.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2014] [Revised: 05/12/2014] [Accepted: 05/12/2014] [Indexed: 11/24/2022]
Abstract
The efficient synthesis of a new series of polyhydroxylated dibenzyl ω-(1H-1,2,3-triazol-1-yl)alkylphosphonates as acyclic nucleotide analogues is described starting from dibenzyl ω-azido(polyhydroxy)alkylphosphonates and selected alkynes under microwave irradiation. Selected O,O-dibenzylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and for cytostatic activity against murine leukemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Compound (1S,2S)-16b exhibited antiviral activity against Influenza A H3N2 subtype (EC50=20μM-visual CPE score; EC50=18μM-MTS method; MCC >100μM, CC50 >100μM) in Madin Darby canine kidney cell cultures (MDCK), and (1S,2S)-16k was active against vesicular stomatitis virus and respiratory syncytial virus in HeLa cells (EC50=9 and 12μM, respectively). Moreover, compound (1R,2S)-16l showed activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50=2.9 and 4μM, respectively) and feline herpes virus in CRFK cells (EC50=4μM) but at the same time it exhibited cytotoxicity toward uninfected cell (MCC⩾4μM). Several other compounds have been found to inhibit proliferation of L1210, CEM as well as HeLa cells with IC50 in the 4-50μM range. Among them compounds (1S,2S)- and (1R,2S)-16l were the most active (IC50 in the 4-7μM range).
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Affiliation(s)
- Iwona E Głowacka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
| | - Jan Balzarini
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
| | - Graciela Andrei
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
| | - Robert Snoeck
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
| | - Dominique Schols
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium
| | - Dorota G Piotrowska
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland
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17
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Clinical Aspects of Hepatitis C Virus Infection. Antiviral Res 2014. [DOI: 10.1128/9781555815493.ch14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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18
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Bankowska E, Balzarini J, Głowacka IE, Wróblewski AE. Design, synthesis, antiviral and cytotoxic evaluation of novel acyclic phosphonate nucleotide analogues with a 5,6-dihydro-1 H-[1,2,3]triazolo[4,5- d]pyridazine-4,7-dione system. MONATSHEFTE FUR CHEMIE 2014; 145:663-673. [PMID: 26166892 PMCID: PMC4494773 DOI: 10.1007/s00706-013-1137-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Accepted: 12/16/2013] [Indexed: 11/26/2022]
Abstract
ABSTRACT A series of diethyl 2-(4,5-dimethoxycarbonyl-1H-1,2,3-triazol-1-yl)alkylphosphonates was synthesised from ω-azidoalkylphosphonates and dimethyl acetylenedicarboxylate and was further transformed into the respective diamides, dihydrazides, and 5,6-dihydro-1H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diones as phosphonate analogues of acyclic nucleosides having nucleobases replaced with substituted 1,2,3-triazoles. All compounds containing P-C-C-triazole or P-C-C-CH2-triazole moieties exist in single conformations in which the diethoxyphosphoryl and substituted 1,2,3-triazolyl or substituted (1,2,3-triazolyl)methyl groups are oriented anti. All phosphonates were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity. They were not cytostatic at 100 μM. GRAPHICAL ABSTRACT
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Affiliation(s)
- Emilia Bankowska
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland
| | - Jan Balzarini
- Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium
| | - Iwona E. Głowacka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland
| | - Andrzej E. Wróblewski
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Lodz, Poland
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19
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Głowacka IE, Balzarini J, Wróblewski AE. The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker. Eur J Med Chem 2013; 70:703-22. [PMID: 24219992 PMCID: PMC7115586 DOI: 10.1016/j.ejmech.2013.10.057] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 10/16/2013] [Accepted: 10/23/2013] [Indexed: 11/13/2022]
Abstract
The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC50 = 17 μM) and feline herpes virus (EC50 = 24 μM) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC50 in the 2.8–12 μM range.
Nucleotide analogues with aliphatic linker between phosphorus and 1,2,3-triazole. Efficient synthesis of 1,2,3-triazole analogues of nucleotides. Antiviral activity and inhibitory effect on the proliferation of CEM cells.
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Affiliation(s)
- Iwona E Głowacka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
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20
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Dong HS, Wang DD, Jin CQ. The Synthesis of (4E
)-N
-(4-chlorophenyl)-5-substituted-2-diazo-3-oxopent-4-enoic Acid Amides. J CHIN CHEM SOC-TAIP 2013. [DOI: 10.1002/jccs.200500141] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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21
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Głowacka IE, Balzarini J, Wróblewski AE. Synthesis of a New Series of Phosphonylated 1,2,3-Triazoles as Acyclic Analogs of Ribavirin. Arch Pharm (Weinheim) 2013; 346:677-87. [DOI: 10.1002/ardp.201300156] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 07/01/2013] [Accepted: 07/10/2013] [Indexed: 11/11/2022]
Affiliation(s)
- Iwona E. Głowacka
- Faculty of Pharmacy, Bioorganic Chemistry Laboratory; Medical University of Łódź; Łódź; Poland
| | - Jan Balzarini
- Rega Institute for Medical Research, KU Leuven; Leuven; Belgium
| | - Andrzej E. Wróblewski
- Faculty of Pharmacy, Bioorganic Chemistry Laboratory; Medical University of Łódź; Łódź; Poland
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22
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Hamada M, Roy V, McBrayer TR, Whitaker T, Urbina-Blanco C, Nolan SP, Balzarini J, Snoeck R, Andrei G, Schinazi RF, Agrofoglio LA. Synthesis and broad spectrum antiviral evaluation of bis(POM) prodrugs of novel acyclic nucleosides. Eur J Med Chem 2013; 67:398-408. [PMID: 23911854 PMCID: PMC7111275 DOI: 10.1016/j.ejmech.2013.06.053] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2013] [Revised: 06/14/2013] [Accepted: 06/20/2013] [Indexed: 11/10/2022]
Abstract
A series of seventeen hitherto unknown ANP analogs bearing the (E)-but-2-enyl aliphatic side chain and modified heterocyclic base such as cytosine and 5-fluorocytosine, 2-pyrazinecarboxamide, 1,2,4-triazole-3-carboxamide or 4-substituted-1,2,3-triazoles were prepared in a straight approach through an olefin acyclic cross metathesis as key synthetic step. All novel compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex virus type 1 and 2, varicella zoster virus, feline herpes virus, human cytomegalovirus, hepatitis C virus (HCV), HIV-1 and HIV-2. Among these molecules, only compound 31 showed activity against human cytomegalovirus in HEL cell cultures with at EC50 of ∼10 μM. Compounds 8a, 13, 14, and 24 demonstrated pronounced anti-HCV activity without significant cytotoxicity at 100 μM.
The synthesis of new acyclonucleoside phosphonates is proposed. Challenging olefin acyclic cross metathesis is the key synthetic step. CuAAC reaction under microwave activation led to substituted-1,2,3-triazoles. Compounds exhibited pronounced anti-HCV activity. Compounds were also evaluated on a wide panel of other viral strains.
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Affiliation(s)
- Manabu Hamada
- Institut de Chimie Organique et Analytique, UMR 7311 CNRS, Université d'Orléans, 45067 Orléans, France
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23
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González-González CA, Fuentes-Benítez A, Cuevas-Yáñez E, Corona-Becerril D, González-Romero C, González-Calderón D. Corey lactone as key precursor for a facile synthesis of novel 1,2,3-triazole carbocyclic nucleosides via Click Chemistry. Tetrahedron Lett 2013. [DOI: 10.1016/j.tetlet.2013.03.069] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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24
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Głowacka IE, Balzarini J, Wróblewski AE. Synthesis and biological evaluation of novel 1,2,3-triazolonucleotides. Arch Pharm (Weinheim) 2013; 346:278-91. [PMID: 23427010 DOI: 10.1002/ardp.201200421] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Accepted: 12/21/2012] [Indexed: 11/09/2022]
Abstract
A general procedure for the preparation of 1,2,3-triazole analogs of nucleosides from diethyl 2-azidoethoxymethyl- and 2-azidoethoxyethylphosphonates was elaborated. The application of microwave irradiation shortened the reaction time to 10 min in comparison to ca. 48 h when 1,3-dipolar cycloadditions were performed under standard conditions. All compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses. None of the compounds were antivirally active at subtoxic concentrations. Compound 17k exhibited moderate inhibitory effects on the proliferation of human T-lymphocyte cells (IC50=64 µM for CEM).
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Affiliation(s)
- Iwona E Głowacka
- Faculty of Pharmacy, Bioorganic Chemistry Laboratory, Medical University of Łódź, Łódź, Poland.
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25
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Li W, Jia Q, Du Z, Wang J. Direct access to triazole-olefins through catalytic cycloaddition of azides to unsaturated aldehydes. Chem Commun (Camb) 2013; 49:10187-9. [DOI: 10.1039/c3cc45306e] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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26
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Driowya M, Puissant A, Robert G, Auberger P, Benhida R, Bougrin K. Ultrasound-assisted one-pot synthesis of anti-CML nucleosides featuring 1,2,3-triazole nucleobase under iron-copper catalysis. ULTRASONICS SONOCHEMISTRY 2012; 19:1132-1138. [PMID: 22595539 DOI: 10.1016/j.ultsonch.2012.04.007] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Revised: 03/29/2012] [Accepted: 04/08/2012] [Indexed: 05/31/2023]
Abstract
A simple and efficient synthesis of modified 1,2,3-triazole nucleosides was developed. The strategy involved sequential one-pot acetylation-azidation-cycloaddition procedure and was found to be highly effective under a cooperative effect of ultrasound activation and iron/copper catalysis. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions. This one-pot procedure provides several advantages such as operational simplicity, high yield, safety and environment friendly protocol. The resulting substituted nucleosides were evaluated for their anticancer activity against K562 chronic myelogenous leukemia (CML) cell line.
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Affiliation(s)
- Mohsine Driowya
- Institut de Chimie de Nice UMR CNRS 7272, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice Cedex 2, France
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27
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Efthymiou T, Gong W, Desaulniers JP. Chemical architecture and applications of nucleic acid derivatives containing 1,2,3-triazole functionalities synthesized via click chemistry. Molecules 2012; 17:12665-703. [PMID: 23103533 PMCID: PMC6268694 DOI: 10.3390/molecules171112665] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2012] [Revised: 10/19/2012] [Accepted: 10/19/2012] [Indexed: 11/16/2022] Open
Abstract
There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC), there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising.
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Affiliation(s)
| | | | - Jean-Paul Desaulniers
- Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe St N, Oshawa, ON L1H 7K4, Canada
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28
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Głowacka IE, Balzarini J, Wróblewski AE. Design, synthesis, antiviral, and cytotoxic evaluation of novel phosphonylated 1,2,3-triazoles as acyclic nucleotide analogues. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2012; 31:293-318. [PMID: 22444192 DOI: 10.1080/15257770.2012.662611] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
The 1,3-dipolar cycloaddition of diethyl 2-azidoethyl-, 3-azidopropyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropylphosphonates with selected N-propargyl nucleobases gave a series of the phosphonylated 1,2,3-triazole acyclonucleosides in which the phosphonate residue and nucleobases were linked by three- and four-carbon chains. Under standard conditions (TMSBr, ethanol), all synthesized O,O-diethylphosphonates were transformed into the respective phosphonic acids. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses. Unfortunately, no antiviral activity was observed at 100 μM.
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Affiliation(s)
- Iwona E Głowacka
- Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Łódź, Łódź, Poland.
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29
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Hou J, Liu X, Shen J, Zhao G, Wang PG. The impact of click chemistry in medicinal chemistry. Expert Opin Drug Discov 2012; 7:489-501. [PMID: 22607210 DOI: 10.1517/17460441.2012.682725] [Citation(s) in RCA: 196] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The copper(I)-catalyzed 1,3-dipolar cycloaddition of alkynes and azides to form 1,2,3-triazoles is the most popular reaction in click chemistry. This reaction is also near-perfect, in terms of its robustness, due to the high degree of reliability and complete specificity. Furthermore, this reaction has been used increasingly in drug discovery, because the formed 1,2,3-triazole can act as both a bioisostere and a linker. AREAS COVERED This review provides an overview of a most important click reaction, 1,3-dipolar cycloadditions of alkynes and azides, in the drug discovery. EXPERT OPINION Click chemistry is a very powerful tool, in the drug discovery, because it is very efficient in the creation of compound libraries through combinatorial methodology. However, the 1,2,3-triazole ring itself is not a commonly used pharmacophore and has rarely been found in marketed drugs, demonstrating that there are still some limitations during the use of 1,2,3-triazole in the molecules of drug candidates. Hopefully, in the next decade, we will witness the emergence of 1,2,3-triazole-bearing drugs on the market as this click reaction is used more and more widely in the drug discovery.
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Affiliation(s)
- Jingli Hou
- Nankai University, State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Tianjin 300071, PR China
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30
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Wang L, Peng S, Danence LJT, Gao Y, Wang J. Amine-Catalyzed [3+2] Huisgen Cycloaddition Strategy for the Efficient Assembly of Highly Substituted 1,2,3-Triazoles. Chemistry 2012; 18:6088-93. [DOI: 10.1002/chem.201103393] [Citation(s) in RCA: 143] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2011] [Revised: 02/14/2012] [Indexed: 11/10/2022]
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31
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Efficient synthesis and in vitro antitubercular activity of 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis. Bioorg Med Chem Lett 2011; 21:7273-6. [PMID: 22061642 DOI: 10.1016/j.bmcl.2011.10.048] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2011] [Revised: 09/06/2011] [Accepted: 10/14/2011] [Indexed: 11/23/2022]
Abstract
Efficient and rapid synthesis of 1,2,3-triazole derivatives has been achieved via Huisgen's 1,3-dipolar cycloaddition between alkyl/arylazides and diethyl/dimethyl acetylenedicarboxylate in excellent yields under solvent-free conditions. The environmentally friendly solvent-free protocol overcomes the limitations associated with the prevailing time-consuming solution phase protocols and affords the triazoles just in 1-3 min. In vitro antitubercular activity of these triazoles was screened against Mycobacterium tuberculosis H(37)Rv strain. Four of the compounds showed MIC in the range of 1.56-3.13 μg/mL proving their potential activity.
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32
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Agalave SG, Maujan SR, Pore VS. Click Chemistry: 1,2,3-Triazoles as Pharmacophores. Chem Asian J 2011; 6:2696-718. [DOI: 10.1002/asia.201100432] [Citation(s) in RCA: 907] [Impact Index Per Article: 64.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Indexed: 12/16/2022]
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33
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Piotrowska DG, Cieślak M, Królewska K, Wróblewski AE. Design, synthesis and cytotoxicity of a new series of isoxazolidines derived from substituted chalcones. Eur J Med Chem 2011; 46:1382-9. [DOI: 10.1016/j.ejmech.2011.01.067] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Revised: 01/27/2011] [Accepted: 01/27/2011] [Indexed: 10/18/2022]
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34
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Głowacka IE, Cieślak M, Piotrowska DG. Synthesis of Novel 1-Hydroxy-2-(1,2,3-triazol-1-yl)ethylphosphonates and 2-Hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates. PHOSPHORUS SULFUR 2011. [DOI: 10.1080/10426507.2010.494646] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Iwona E. Głowacka
- a Bioorganic Chemistry Laboratory, Faculty of Pharmacy , Medical University of Łódź , Poland
| | - Marcin Cieślak
- b Department of Bioorganic Chemistry , Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences , Łódź , Poland
| | - Dorota G. Piotrowska
- a Bioorganic Chemistry Laboratory, Faculty of Pharmacy , Medical University of Łódź , Poland
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35
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Piotrowska DG, Cieślak M, Królewska K, Wróblewski AE. Design, Synthesis and Cytotoxicity of a New Series of Isoxazolidine Based Nucleoside Analogues. Arch Pharm (Weinheim) 2011; 344:301-10. [DOI: 10.1002/ardp.201000282] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Revised: 11/04/2010] [Accepted: 11/05/2010] [Indexed: 11/08/2022]
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36
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Maarouf AR, Farahat AA, Selim KB, Eisa HM. Synthesis and antiviral activity of benzimidazolyl- and triazolyl-1,3,5-triazines. Med Chem Res 2011. [DOI: 10.1007/s00044-011-9574-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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37
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Montagu A, Roy V, Balzarini J, Snoeck R, Andrei G, Agrofoglio LA. Synthesis of new C5-(1-substituted-1,2,3-triazol-4 or 5-yl)-2'-deoxyuridines and their antiviral evaluation. Eur J Med Chem 2010; 46:778-86. [PMID: 21232828 DOI: 10.1016/j.ejmech.2010.12.017] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Revised: 12/09/2010] [Accepted: 12/10/2010] [Indexed: 02/05/2023]
Abstract
The synthesis and antiviral evaluation of a series of C5-(1,4- and 1,5-disubstituted-1,2,3-triazolo)-nucleoside derivatives is described. The key steps of this synthesis are regioselective Huisgen's 1,3-dipolar cycloaddition, using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) under microwave activation. Some compounds among the 5a-l series possess activity against herpes simplex viruses 1 and 2, varicella-zoster virus, human cytomegalovirus and vaccinia virus. Their cytostatic activities were determined against murine leukemia cells, human T-lymphocyte cells and cervix carcinoma cells. Compounds were also evaluated on a wide panel of RNA viruses, including Vesicular stomatitis virus, influenza viruses type A (H1N1 and H3N2) and B in MDCK cell cultures, parainfluenza-3 virus, reovirus-1, Sindbis virus and Punta Toro virus in Vero cell cultures and Vesicular stomatitis, Coxsackie B4 and respiratory syncytial virus, with no specific antiviral effect.
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Affiliation(s)
- Aurélien Montagu
- Institut de Chimie Organique et Analytique, UMR 6005, Université d'Orléans, 45067 Orléans, France
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38
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Elayadi H, Smietana M, Pannecouque C, Leyssen P, Neyts J, Vasseur JJ, Lazrek HB. Straightforward synthesis of triazoloacyclonucleotide phosphonates as potential HCV inhibitors. Bioorg Med Chem Lett 2010; 20:7365-8. [PMID: 21051229 DOI: 10.1016/j.bmcl.2010.10.046] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Revised: 10/11/2010] [Accepted: 10/12/2010] [Indexed: 10/18/2022]
Abstract
Preparation of several triazoloacyclic nucleoside phosphonates is described. The key step of the synthesis involves a copper(I)-catalysed azide-alkyne 1,3-dipolar cycloaddition between azidoalkylphosphonates and propargylated nucleobases. The antiviral properties of these new analogues have been evaluated and revealed interesting potencies.
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Affiliation(s)
- Hanane Elayadi
- Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-UM1-UM2, Université Montpellier II, Montpellier, France
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39
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Synthesis of conformationally restricted 1,2,3-triazole-substituted ethyl β- and γ-aminocyclopentanecarboxylate stereoisomers. Multifunctionalized alicyclic amino esters. Tetrahedron 2010. [DOI: 10.1016/j.tet.2010.03.030] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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40
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Lin J, Roy V, Wang L, You L, Agrofoglio LA, Deville-Bonne D, McBrayer TR, Coats SJ, Schinazi RF, Eriksson S. 3'-(1,2,3-Triazol-1-yl)-3'-deoxythymidine analogs as substrates for human and Ureaplasma parvum thymidine kinase for structure-activity investigations. Bioorg Med Chem 2010; 18:3261-9. [PMID: 20378362 PMCID: PMC7744269 DOI: 10.1016/j.bmc.2010.03.023] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2009] [Revised: 03/04/2010] [Accepted: 03/11/2010] [Indexed: 11/23/2022]
Abstract
The pathogenic mycoplasma Ureaplasma parvum (Up) causes opportunistic infections and relies on salvage of nucleosides for DNA synthesis and Up thymidine kinase (UpTK) provides the necessary thymidine nucleotides. The anti-HIV compound 3 -azido-3'-deoxythymidine (AZT) is a good substrate for TK. Methods for a rapid and efficient synthesis of new 3'-alpha-[1,2,3]triazol-3'-deoxythymidine analogs from AZT under Huisgen conditions are described. Thirteen 3'-analogues were tested with human cytosolic thymidine kinase (hTK1) and UpTK. The new analogs showed higher efficiencies (K(m)/V(max) values) in all cases with UpTK than with hTK1. Still, hTK1 was preferentially inhibited by 9 out of 10 tested analogs. Structural models of UpTK and hTK1 were constructed and used to explain the kinetic results. Two different binding modes of the nucleosides within the active sites of both enzymes were suggested with one predominating in the bacterial enzyme and the other in hTK1. These results will aid future development of anti-mycoplasma nucleosides.
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Affiliation(s)
- Jay Lin
- Dpt. Anatomy, Physiology and Biochemistry, Veterinary Medical Biochemistry, Swedish University Agricultural Sciences, Uppsala, Sweden
| | - Vincent Roy
- Institut de Chimie Organique et Analytique, CNRS UMR 6005, Université d’Orléans, 45067 Orléans Cedex 2, France
| | - Liya Wang
- Dpt. Anatomy, Physiology and Biochemistry, Veterinary Medical Biochemistry, Swedish University Agricultural Sciences, Uppsala, Sweden
| | - Li You
- Institut de Chimie Organique et Analytique, CNRS UMR 6005, Université d’Orléans, 45067 Orléans Cedex 2, France
| | - Luigi A. Agrofoglio
- Institut de Chimie Organique et Analytique, CNRS UMR 6005, Université d’Orléans, 45067 Orléans Cedex 2, France
| | - Dominique Deville-Bonne
- Laboratoire d’ Enzymologie Moléculaire et Fonctionnelle, Université Pierre et Marie Curie, Paris, France
| | - Tamara R. McBrayer
- Center for AIDS Research, Lab. Biochem. Pharmacol., Dpt. Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, GA 30033, USA
- RFS Pharma, LLC, 1860 Montreal Road, Tucker, GA 30084, USA
| | | | - Raymond F. Schinazi
- Center for AIDS Research, Lab. Biochem. Pharmacol., Dpt. Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, GA 30033, USA
| | - Staffan Eriksson
- Dpt. Anatomy, Physiology and Biochemistry, Veterinary Medical Biochemistry, Swedish University Agricultural Sciences, Uppsala, Sweden
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41
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Głowacka IE. Synthesis of enantiomerically pure diethyl (R)- and (S)-2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates. ACTA ACUST UNITED AC 2009. [DOI: 10.1016/j.tetasy.2009.09.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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42
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Diab SA, Hienzch A, Lebargy C, Guillarme S, Pfund E, Lequeux T. Synthesis of fluorophosphonylated acyclic nucleotide analogues via copper(I)-catalyzed Huisgen 1-3 dipolar cycloaddition. Org Biomol Chem 2009; 7:4481-90. [PMID: 19830299 DOI: 10.1039/b912724k] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Preparation of several acyclonucleosides containing both a difluoromethylphosphonate group and a triazole moiety is described starting from a difluorophosphonosulfide. The key step of the synthesis involves a copper(I)-catalyzed Huisgen 1-3 dipolar cycloaddition between difluorophosphonylated azides and propargylated nucleobases derived from thymine and 2-amino-6-chloropurine.
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Affiliation(s)
- Sonia Amel Diab
- Laboratoire de Chimie Moléculaire et Thioorganique, ENSICAEN, Université de Caen Basse-Normandie, UMR-CNRS 6507, FR3038, 6 Bd du Maréchal Juin, 14050, Caen Cedex, France
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43
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Broggi J, Kumamoto H, Berteina-Raboin S, Nolan SP, Agrofoglio LA. Click Azide-Alkyne Cycloaddition for the Synthesis of D-(-)-1,4-Disubstituted Triazolo-Carbanucleosides. European J Org Chem 2009. [DOI: 10.1002/ejoc.200801124] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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44
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Broggi J, Joubert N, Díez-González S, Berteina-Raboin S, Zevaco T, Nolan SP, Agrofoglio LA. Synthesis of (±)-1,2,3-triazolo-3′-deoxy-4′-hydroxymethyl carbanucleosides via ‘click’ cycloaddition. Tetrahedron 2009. [DOI: 10.1016/j.tet.2008.11.065] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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45
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Novel functionalized cispentacin derivatives. Synthesis of 1,2,3-triazole-substituted 2-aminocyclopentanecarboxylate stereoisomers. ACTA ACUST UNITED AC 2008. [DOI: 10.1016/j.tetasy.2008.11.035] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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46
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Pradere U, Roy V, McBrayer TR, Schinazi RF, Agrofoglio LA. Preparation of ribavirin analogues by copper- and ruthenium-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Tetrahedron 2008; 64:9044-9051. [PMID: 34321698 PMCID: PMC8315236 DOI: 10.1016/j.tet.2008.07.007] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
In this study, we described the synthesis of 1,4- and 1,5-disubstituted-1,2,3-triazolo-nucleosides from various alkynes with 1'-azido-2',3',5'-tri-O-acetylribose using either copper-catalyzed azide-alkyne cycloaddition (CuAAC) or ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC), respectively. Optimized RuAAC conditions were realized with the commercially available [Cp*RuCl(PPh3)2] under microwave heating, which allows a significant acceleration of the reaction times (from 6 h to 5 min). This reaction can work under water-containing system. RuAAC and CuAAC are useful tools for the synthesis of 1,2,3-triazolyl-nucleosides small libraries.
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Affiliation(s)
- Ugo Pradere
- Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 6005, BP 6759, 45067 Orléans, France
| | - Vincent Roy
- Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 6005, BP 6759, 45067 Orléans, France
| | - Tamara R. McBrayer
- Emory University School of Medicine, Atlanta, GA 30033, USA
- Veterans Affairs Medical Center, Atlanta, GA 30033, USA
| | - Raymond F. Schinazi
- Emory University School of Medicine, Atlanta, GA 30033, USA
- Veterans Affairs Medical Center, Atlanta, GA 30033, USA
| | - Luigi A. Agrofoglio
- Institut de Chimie Organique et Analytique, Université d’Orléans, UMR CNRS 6005, BP 6759, 45067 Orléans, France
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47
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Li ZH, Li CM, Ling P, Shen FH, Chen SH, Liu CC, Yu CK, Chen SH. Ribavirin reduces mortality in enterovirus 71-infected mice by decreasing viral replication. J Infect Dis 2008; 197:854-7. [PMID: 18279075 PMCID: PMC7109938 DOI: 10.1086/527326] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Enterovirus 71 (EV71) causes fatal encephalitis in young children. However, there is no effective antiviral drug available for infected patients. Ribavirin is currently used for the treatment of several RNA virus infections clinically, so its anti-EV71 efficacy was evaluated. In vitro results showed that ribavirin effectively reduced the viral yields (with an IC50 of 65 μg/mL) and virus-induced cytopathic effect in human and mouse cell lines. In vivo results showed that ribavirin reduced the mortality, morbidity, and subsequent paralysis sequelae in infected mice by decreasing viral loads in tissues. Thus, ribavirin could be a potential anti-EV71 drug
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Affiliation(s)
- Zhao-Hong Li
- Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University,Taiwan, Republic of China
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48
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Oppilliart S, Mousseau G, Zhang L, Jia G, Thuéry P, Rousseau B, Cintrat JC. 1-Protected 5-amido 1,2,3-triazoles via ruthenium-catalyzed [3+2] cycloaddition of azides and ynamides. Tetrahedron 2007. [DOI: 10.1016/j.tet.2007.06.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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49
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50
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Zhan T, Lou H. Synthesis of azole nucleoside analogues of d-pinitol as potential antitumor agents. Carbohydr Res 2007; 342:865-9. [PMID: 17258696 DOI: 10.1016/j.carres.2007.01.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2006] [Revised: 12/19/2006] [Accepted: 01/09/2007] [Indexed: 11/27/2022]
Abstract
A convenient strategy is reported for the synthesis of azole nucleoside analogues of D-pinitol (=3-O-methyl-D-chiro-inositol). The key intermediate 3-O-methyl-4,5-epoxy-D-chiro-inositol was obtained in excellent yield via an epoxidation from mono-methanesulfonate of D-pinitol. The process of opening of the epoxy ring by azole-bases appeared strongly regioselective in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene. All newly synthesized carbocyclic azole nucleosides were assayed against lung and bladder cancer in vitro. Only the triazole and benzotriazole nucleoside analogues inhibited the growth of human lung cancer cell lines (PG) with EC(50) of 11.3 and 22.6 microM, respectively, and showed much less inhibitory activity against human bladder cell lines (T(24)).
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Affiliation(s)
- Tianrong Zhan
- College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, People's Republic of China.
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