Synthesis, Anti-Varicella-Zoster Virus and Anti-Cytomegalovirus Activity of 4,5-Disubstituted 1,2,3-(1H)-Triazoles
| Autor: | Dominique Schols, Bei Yang, Qin-Pei Wu, Ning-Ning Liu, Robert Snoeck, Yong-Wei Wu, Graciela Andrei, Zhuo-Yong Zhang, Yu-Hong Xiang, Xue Chen, Yi-ning Wen, Wei-yuan Yuan, Zhen Jiang |
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| Rok vydání: | 2019 |
| Předmět: |
Human cytomegalovirus
Herpesvirus 3 Human viruses Cytomegalovirus Microbial Sensitivity Tests Drug resistance medicine.disease_cause Antiviral Agents 01 natural sciences Virus Structure-Activity Relationship 03 medical and health sciences Drug Discovery medicine Humans Cells Cultured 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Varicella zoster virus virus diseases Fibroblasts Triazoles medicine.disease Virology In vitro 0104 chemical sciences Herpes simplex virus Thymidine kinase |
| Zdroj: | Medicinal Chemistry. 15:801-812 |
| ISSN: | 1573-4064 |
| Popis: | Background: Clinical drugs for herpesvirus exhibit high toxicity and suffer from significant drug resistance. The development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action is greatly required. Objective: Novel inhibitors against herpesvirus with different mechanisms of action from that of clinical drugs. Methods: A series of novel 5-(benzylamino)-1H-1,2,3-triazole-4-carboxamides were efficiently synthesized and EC50 values against Human Cytomegalovirus (HCMV), Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) were evaluated in vitro. Results: Some compounds present antiviral activity. Compounds 5s and 5t are potent against both HCMV and VZV. Compounds 5m, 5n, 5s, and 5t show similar EC50 values against both TK+ and TK− VZV strains. Conclusion: 5-(Benzylamino)-1H-1, 2,3-triazole-4-carboxamides are active against herpesviruses and their activity is remarkably affected by the nature and the position of substituents in the benzene ring. The results indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. Their mechanisms of action may differ from those of the clinic anti-herpesvirus drugs. |
| Databáze: | OpenAIRE |
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