Design, synthesis and biological evaluation of 1,3,4-triazole-3-acetamide derivatives as potent neuraminidase inhibitors

Abstract

Neuraminidase (NA) is an ideal target for the development of anti-influenza drugs. In this paper, ZINC06057848 was screened out as a hit compound by docking-based virtual screening and molecular dynamics (MD) simulation. The modification and optimization of hit ZINC06057848 resulted in the discovery of a series of novel 1,3,4-triazole-containing NA inhibitors (5a-5j). Compound 5c exerts the best inhibitory activity (IC₅₀ = 0.11 µM) against NA, which is comparable to the positive control oseltamivir carboxylate (OSC) (IC₅₀ = 0.10 µM). Molecular docking analysis indicates that the good efficacy of inhibitor 5c may be attributed to the furan and triazole rings extending into 430-cavity and the ethylbenzene part occupying the active site. The results of this work may help in the development of new NA inhibitors.

Keywords: 430-cavity; Influenza; Neuraminidase inhibitors; Triazole derivatives; Virtual screening.