Synthesis, Antileishmanial Activity and Molecular Docking Study of a Series of Dihydropyridine Derivatives

Abstract

A series of 1,4-dihydropyridine (DHP) derivatives have been synthesized and evaluated against both promastigote and amastigotes forms. All compounds showed higher activity than the reference drug amphotericin B. However, they exhibited less activity than the reference drug glucantime, except compound 4e. These compounds showed excellent anti-promastigote and amastigote activities in range of low nanomolar and low micromolar, respectively. Among the screened compounds, 4d was found as the most potent compounds against promastigote form with EC50 value of 0.0001 nM and compound 4e was the most potent compound against amastigote form with EC50 value of 2.38 µM. Based on CC50 results, synthesized compounds were found nontoxic to macrophages. The study demonstrated that, the position and nature of the substituents on phenyl ring of C4 in the DHP ring and the length of the chain belonging to the ester groups influences the biological activity of these compounds. Based on docking studies, it was proposed that compounds 4d and 4e form key interactions with regions of PTR1 enzyme. © 2022 Taylor & Francis Group, LLC.