Synthesis and biological evaluation of 2-acetamidothiophene-3-carboxamide derivatives against Leishmania donovani

Abstract

A high-throughput (HTS) and high-content screening (HCS) campaign of a commercial library identified 2-acetamidothophen-3-carboxamide as a novel scaffold for developing new anti-leishmanial agents. A series of chemical modifications were performed to study the structure–activity relationship (SAR) and in vitro anti-leishmanial activities were evaluated using biological assays of not only extracellular promastigotes but also intracellular amastigotes. Compound 6a showed promising anti-amastigote activity (EC₅₀ = 6.41 μM) against L. donovani without any cytotoxicity (CC₅₀ > 50 μM) towards human macrophages.