Computer-Aided Drug Design Studies in Association with in vitro Antileishmanial Tests for New Chalcones

• Published in: Journal of the Brazilian Chemical Society Vol. 36; no. 2
• Main Authors: da Silva, Gleice, Santos, Francisnaira, Leite, Fernando, Acevedo, Chonny, de Sousa, Natália, Grimaldi, Gabriela, Soares, Milena, Guimarães, Elisalva, Scotti, Marcus, Rodrigues, Luis Cezar, Mendonça Júnior, Francisco, Campana, Eloísa, Barbosa Filho, José, Guimarães, Hemerson, Guerra, Felipe
• Format: Journal Article
• Language: English; Portuguese
• Published: Sociedade Brasileira de Química 2025
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; MolPredictX; pharmacological activity; homology modeling; molecular docking; flavonoids; computer-aided drug design
• ISSN: 0103-5053; 1678-4790; 1678-4790
• DOI: 10.21577/0103-5053.20240135

In silico and in vitro tests can reveal promising anti-leishmania activity for natural products and their derivatives. The aim of this study was to investigate in silico the pharmacological activities of potential new chalcones and their leishmanicidal potential in vitro. The in silico study was carried out using the PASS, MolPredictX and Molegro Virtual Docker 6.0 programs. Antiparasitic activity was assessed in axenic promastigote and amastigote forms of Leishmania braziliensis. The cytotoxicity tests used the J77G8 cell line. The chalcones exhibited 50% cytotoxic concentration values (CC50) values > 50 μM. Chalcone 4 (named FERAI) presented the best activity with concentration for 50% of promastigotes and intracellular parasites forms (EC50) of 9.75 ± 1.7 and 10.13 ± 1.7 μM for promastigote and amastigote, respectively. Reactive oxygen species (ROS) testing presented increased ROS levels in the parasite at the FERAI concentrations of 10 μM (56.33%), 20 μM (61.76%) and 30 μM (67.13%). Molecular docking revealed interactions (binding energy) between FERAI and the enzymes UDP-glycosyl pyrophosphorylase (-56.8384), dihydroorotate-dehydrogenase (-132.276) and trypanothione-reductase (-151.281). Our results demonstrated the anti-leishmanial activity of chalcones, especially FERAI, with a noted raising of ROS levels in the parasite. Molecular docking revealed dihydroorotate dehydrogenase and trypanothione reductase as potential pharmacological targets for FERAI.