FERAI, a novel brominated chalcone, induces ultrastructural alterations and apoptosis like-death in Leishmania braziliensis

Abstract

Chalcones hold significant potential as bioactive agents due to their simple chemical structure and the possibility of generating more potent derivatives through strategic structural modifications. In a previous study, our research group evaluated the in vitro antileishmanial activity of (E)-1-(benzo[d][1,3]dioxol-5-yl)-3-(3‑bromo-4-ethoxy-5-methoxyphenyl)prop‑2-en-1-one (FERAI) against Leishmania braziliensis promastigotes and amastigotes. The present study aimed to investigate the mechanisms of action of this compound in L. braziliensis parasites. Ultrastructural changes were examined using scanning and transmission electron microscopy. Cell death patterns and mitochondrial membrane potential were assessed by flow cytometry. Scanning electron microscopy revealed morphological alterations in promastigotes, including cell body retraction and plasma membrane disruption. Transmission electron microscopy showed the presence of lipid inclusions, mitochondrial alterations, nuclear swelling, and flagellar loss. In addition, FERAI induced mitochondrial membrane depolarization and triggered apoptotic cell death in L. braziliensis promastigotes. Collectively, these findings suggest that mitochondrial depolarization and direct morphological damage to the parasite, followed by programmed cell death, are central mechanisms of FERAI action against L. braziliensis promastigotes. The elucidation of FERAI's mechanisms of action highlights its potential as a promising candidate for the development of new drugs against leishmaniasis.