New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling.

Autor: da Silva EF; Phytochemistry and Organic Synthesis Laboratory, School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Antunes Fernandes KH; Clinical and Immunology Laboratory, Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil., Diedrich D; Phytochemistry and Organic Synthesis Laboratory, School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Gotardi J; Phytochemistry and Organic Synthesis Laboratory, School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Freire Franco MS; Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-020, Brazil., Tomich de Paula da Silva CH; Laboratory of Computational Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP 14040-020, Brazil., Duarte de Souza AP; Clinical and Immunology Laboratory, Biomedical Research Institute, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil., Baggio Gnoatto SC; Phytochemistry and Organic Synthesis Laboratory, School of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Jazyk: angličtina
Zdroj: Beilstein journal of organic chemistry [Beilstein J Org Chem] 2022 Nov 09; Vol. 18, pp. 1524-1531. Date of Electronic Publication: 2022 Nov 09 (Print Publication: 2022).
DOI: 10.3762/bjoc.18.161
Abstrakt: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in infants. Currently, ribavirin, a nucleoside analog containing a 1,2,4-triazole-3-carboxamide moiety, is a first-line drug for its treatment, however, its clinical use has been limited due to its side effects. Here, we designed two new nitroaryl-1,2,3-triazole triterpene derivatives as novel anti-RSV drugs. Their anti-RSV and cytotoxic activity were evaluated in vitro, RSV protein F gene effects by RT-PCR and molecular modeling with inosine monophosphate dehydrogenase (IMPDH) were performed. Compound 8 was the best performing compound, with an EC 50 value of 0.053 μM, a TI of 11160.37 and it inhibited hRSV protein F gene expression by approximately 65%. Molecular docking showed a top-ranked solution located in the same region occupied by crystallographic ligands in their complex with IMPDH. The results obtained in this study suggest that compound 8 might be a new anti-RSV candidate.
(Copyright © 2022, da Silva et al.)
Databáze: MEDLINE
Externí odkaz: