Open AccessDiscovery of novel West Nile Virus protease inhibitor based on isobenzonafuranone and triazolic derivatives of eugenol and indan-1,3-dione scaffolds
Author(s) -
André Silva de Oliveira,
Poliana Aparecida Rodrigues Gazolla,
Ana Flávia C. da S. Oliveira,
Wagner Luiz Pereira,
Lívia Cristina de Souza Viol,
Angélica Faleiros da Silva Maia,
Edjon G. Santos,
Ítalo E. P. da Silva,
Tiago Antônio de Oliveira Mendes,
Antônio Alberto da Silva,
Roberto Sousa Dias,
Cynthia C. da Silva,
Marcelo D. Polêto,
Róbson Ricardo Teixeira,
Sérgio Oliveira de Paula
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0223017
Subject(s) - eugenol , protease , chemistry , ns3 , stereochemistry , west nile virus , combinatorial chemistry , virology , virus , enzyme , biochemistry , biology , organic chemistry
The West Nile Virus (WNV) NS2B-NS3 protease is an attractive target for the development of therapeutics against this arboviral pathogen. In the present investigation, the screening of a small library of fifty-eight synthetic compounds against the NS2-NB3 protease of WNV is described. The following groups of compounds were evaluated: 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3 H )-ones; eugenol derivatives bearing 1,2,3-triazolic functionalities; and indan-1,3-diones with 1,2,3-triazolic functionalities. The most promising of these was a eugenol derivative, namely 4-(3-(4-allyl-2-methoxyphenoxy)-propyl)-1-(2-bromobenzyl)-1 H -1,2,3-triazole ( 35 ), which inhibited the protease with IC 50 of 6.86 μ mol L -1 . Enzyme kinetic assays showed that this derivative of eugenol presents competitive inhibition behaviour. Molecular docking calculations predicted a recognition pattern involving the residues His 51 and Ser 135 , which are members of the catalytic triad of the WNV NS2B-NS3 protease.