Brominated chalcones as promising antileishmanial agents

Abstract

Leishmaniasis is a group of diseases caused by protozoa of the genus Leishmania. They are considered neglected diseases and are endemic to tropical and subtropical regions, affecting thousands of people annually. Leishmaniasis has a wide global distribution, present on four continents. Various drugs have been used to control leishmaniasis; however, obstacles such as high toxicity to patients and the occurrence of resistance have led to the search for alternatives. Chalcones are α, β-unsaturated ketones that can occur in the secondary metabolism of plants or can be obtained through organic synthesis. In this study, 21 chalcones brominated were synthesized via the Claisen-Schmidt condensation synthesis and characterized by UHRMS and NMR. The biological activity was evaluated for antiprotozoal potential against Leishmania amazonensis and cytotoxicity against L929 fibroblasts. Eighteen chalcones showed viability inhibition rates above 80 % at a concentration of 50 µM. Six chalcones demonstrated IC50 values ranging from 6.33 ± 0.70 µM to 23.95 ± 2.94 µM and maintained 70 % viability in L929 fibroblasts at 50 µM. The (E)-1-(4-bromophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one, with a trimethoxylation at positions 2, 4, and 5 of ring B and a bromine substituent at position 4 of ring A, exhibited the lowest IC50 value (6.33 µM). These results indicate that these brominated chalcones have potential for studies aiming at the development of new drugs for leishmaniasis control.