In vitro and in silico evaluation of the anti-leishmania activity of synthetic chalcones

• Published in: Natural product research pp. 1 - 12
• Main Authors: Leite, Fernando Ferreira, Rodrigues, Luis Cezar, Oliveira, Bruno Hanrry Melo de, Duarte, Gabrielly Diniz, Leite Ferreira, Maria Denise, Sousa, Natália Ferreira de, Vanderley, Shayenne Eduarda Ramos, Cardoso, Leonardo Lima, Keesen, Tatjana Souza Lima, Araújo, Rodrigo Santos Aquino de, Scotti, Luciana, Scotti, Marcus Tullius, Mendonça-Junior, Francisco Jaime Bezerra
• Format: Journal Article
• Language: English
• Published: England 11.09.2024
• Subjects: Chalcones; molecular docking; molecular dynamics; cytotoxicity; anti-leishmania activity
• ISSN: 1478-6419; 1478-6427; 1478-6427
• DOI: 10.1080/14786419.2024.2401499

Leishmaniasis is a group of neglected, vector-borne infectious diseases that affect millions of people around the world. The medications available for its treatment, especially in cases of visceral leishmaniasis, are old, outdated and have serious side effects. In this work, 10 chalcones were synthesised and evaluated against promastigotes and axenic amastigotes of . Compounds CP04 and CP06 were the most promising, respectively presenting IC values = 13.64 ± 0.25 and 11.19 ± 0.22 µM against promastigotes, and IC = 18.92 ± 0.05 and 22.42 ± 0.05 µM against axenic amastigotes. Only compound CP04 did not show cytotoxicity against peripheral blood mononuclear cells (PBMCs). Molecular docking studies conducted with sterol 14-alpha demethylase (CYP-51) (PDB: 3L4D) and trypanothione reductase (PDB: 5EBK) enzymes from evidenced the great affinity of compound CP04 for these targets, presenting Moldock score values of -94.0758 and -50.5692 KJ/mol .