Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents

Abstract

A series of ( Z )-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a–4f ) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g–4l ). Among the latter, two aurones possessing a 2′-methoxy or a 2′-methyl group (compounds 4i and 4j ) exhibit potent antileishmanial activity ( IC 50 = 1.3 ± 0.1 μ M and IC 50 = 1.6 ± 0.2 μ M, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index.