ABSTRACT
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.
Subject(s)
Antiviral Agents/pharmacology , Cytomegalovirus/drug effects , Herpesvirus 3, Human/drug effects , Triazoles/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Cells, Cultured , Dose-Response Relationship, Drug , Fibroblasts/drug effects , Humans , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
BACKGROUND: All of the clinical drugs for herpesvirus infections exhibit high toxicity and suffer from significant drug-resistantance. There is a great need for the development of new, effective, and safe anti-herpesvirus agents with different mechanisms of action. METHODS: A series of novel 5-(benzylthio)-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 possess antiviral activity. Compound 7f exhibits promising inhibitory activity against both HCMV and VZV. Our results also indicate that these derivatives are independent of the viral thymidine kinase (TK) for activation, which is indispensable for current drugs. CONCLUSION: 4,5-Bissubstiuted triazoles are active against herpesviruses and the nature and the position of substituents in the benzene ring remarkably affect their activity, such as bromo, cyano and cyanovynil substituents. Future studies should be undertaken to investigate the mechanism of action of these compounds.
Subject(s)
Antiviral Agents/pharmacology , Cytomegalovirus/drug effects , Herpesvirus 3, Human/drug effects , Triazoles/pharmacology , Acyclovir/pharmacology , Antiviral Agents/chemical synthesis , Bromodeoxyuridine/analogs & derivatives , Bromodeoxyuridine/pharmacology , Cidofovir , Cytosine/analogs & derivatives , Cytosine/pharmacology , Ganciclovir/pharmacology , Herpesvirus 1, Human/drug effects , Herpesvirus 2, Human/drug effects , Organophosphonates/pharmacology , Thymidine Kinase/metabolism , Triazoles/chemical synthesisABSTRACT
A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity.