Brominated chalcones as promising antileishmanial agents

Area of Science:

• Medicinal Chemistry
• Parasitology
• Drug Discovery

Background:

• Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa, prevalent globally and posing a significant public health challenge.
• Existing treatments for leishmaniasis face limitations due to high toxicity and the emergence of drug resistance, necessitating the development of novel therapeutic agents.
• Chalcones, a class of natural or synthetic compounds, are being explored for their diverse biological activities, including antiparasitic potential.

Purpose of the Study:

• To synthesize and characterize a series of novel brominated chalcones.
• To evaluate the antiprotozoal activity of these synthesized chalcones against Leishmania amazonensis.
• To assess the cytotoxicity of the active chalcones against L929 fibroblasts to determine their therapeutic potential.

Main Methods:

• Twenty-one brominated chalcones were synthesized using the Claisen-Schmidt condensation reaction.
• Compounds were characterized using high-resolution mass spectrometry (UHRMS) and nuclear magnetic resonance (NMR) spectroscopy.
• Antiprotozoal activity was assessed against Leishmania amazonensis, and cytotoxicity was evaluated using L929 fibroblast cell lines.

Main Results:

• Eighteen of the synthesized chalcones demonstrated significant inhibition of Leishmania amazonensis viability (>80% at 50 µM).
• Six chalcones exhibited potent antiprotozoal activity with IC50 values ranging from 6.33 µM to 23.95 µM.
• These six compounds maintained high viability (>70%) in L929 fibroblasts at 50 µM, indicating a favorable safety profile.

Conclusions:

• The synthesized brominated chalcones possess significant antiprotozoal activity against Leishmania amazonensis.
• The compound (E)-1-(4-bromophenyl)-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one showed the most promising activity with the lowest IC50 value.
• These findings highlight the potential of these novel brominated chalcones as lead compounds for the development of new anti-leishmaniasis drugs.