Design, Synthesis, and Antiviral Activities of New Benzotriazole-Based Derivatives.

Content Provider	Europe PMC
Author	Ibba, Roberta Corona, Paola Nonne, Francesca Caria, Paola Serreli, Gabriele Palmas, Vanessa Riu, Federico Sestito, Simona Nieddu, Maria Loddo, Roberta Sanna, Giuseppina Piras, Sandra Carta, Antonio
Editor	Massari, Serena
Copyright Year	2023
Abstract	Several human diseases are caused by enteroviruses and are currently clinically untreatable, pushing the research to identify new antivirals. A notable number of benzo[d][1,2,3]triazol-1(2)-yl derivatives were designed, synthesized, and in vitro evaluated for cytotoxicity and antiviral activity against a wide spectrum of RNA positive- and negative-sense viruses. Five of them (11b, 18e, 41a, 43a, 99b) emerged for their selective antiviral activity against Coxsackievirus B5, a human enteroviruses member among the Picornaviridae family. The EC50 values ranged between 6 and 18.5 μM. Among all derivatives, compounds 18e and 43a were interestingly active against CVB5 and were selected to better define the safety profile on cell monolayers by transepithelial resistance test (TEER). Results indicated compound 18e as the hit compound to investigate the potential mechanism of action by apoptosis assay, virucidal activity test, and the time of addition assay. CVB5 is known to be cytotoxic by inducing apoptosis in infected cells; in this study, compound 18e was proved to protect cells from viral infection. Notably, cells were mostly protected when pre-treated with derivative 18e, which had, however, no virucidal activity. From the performed biological assays, compound 18e turned out to be non-cytotoxic as well as cell protective against CVB5 infection, with a mechanism of action ascribable to an interaction on the early phase of infection, by hijacking the viral attachment process.
Volume Number	16
PubMed Central reference number	PMC10054465
Issue Number	3
PubMed reference number	36986528
Journal	Pharmaceuticals (Basel)
e-ISSN	14248247
DOI	10.3390/ph16030429
Language	English
Publisher	MDPI
Publisher Date	2023-03-11
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	benzotriazoles antiviral compounds enterovirus coxsackievirus B5 RNA-virus Picornaviridae
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmaceutical Science Molecular Medicine