Asymmetric synthesis of novel triazole derivatives and their in vitro antiviral activity and mechanism of action

Abstract

In this study, forty-four chiral triazole derivatives have been prepared via asymmetric synthesis, and which has been successfully characterized by typical spectroscopic techniques including ¹H NMR, ¹³C NMR, EI-MS, elemental analysis and optical rotations. Their in vitro antiviral activities against EV71 and CVB3 were fully investigated in cell-based assays. It was observed that 13 synthetic triazole derivatives inhibited the CPE of EV71 on RD cells, with EC_50S in the 5.3-15.9 μg/ml range and corresponding SIs of 4.0-27.6, while 17 triazole derivatives showed antiviral activities against CVB3, with EC_50S in the 4.7-15.1 μg/ml range and the corresponding SIs of 3.7-14.5. In addition, in some cases, the respective enantiomers showed significantly selective inhibitory effect against EV71, most notably for the enantiomers 9(R) and 10(S), 42(R) and 43(S), which presented an obvious activity difference. The most potential molecules are the compounds 10 and 43 with S-configuration, and which exhibit good SI values compared with the control Ribavirin.

Keywords: Antiviral activity; Chiral triazole; Coxsackievirus B3; Enterovirus 71; Mechanism of action; Synthesis.