Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp

Haruna Luz Barazorda-Ccahuana, Luis Daniel Goyzueta-Mamani, Mayron Antonio Candia Puma, Camila Simões de Freitas, Grasiele de Sousa Vieria Tavares, Daniela Pagliara Lage, Eduardo Antonio Ferraz Coelho, Miguel Angel Chávez-Fumagalli

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Resumen

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the new approaches and advances to fight the disease, there are no effective therapies. Methods: Hence, this study aims to screen for natural products' structural analogs as new drug candidates against leishmaniasis. We applied Computer-aided drug design (CADD) approaches, such as virtual screening, molecular docking, molecular dynamics simulation, molecular mechanics–generalized Born surface area (MM–GBSA) binding free estimation, and free energy perturbation (FEP) aiming to select structural analogs from natural products that have shown anti-leishmanial and anti-arginase activities and that could bind selectively against the Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, and malvidin showed good results against arginase targets from three parasite species and negative results for potential toxicities. The echioidinin and malvidin ligands generated interactions in the active center at pH 2.0 conditions by MM-GBSA and FEP methods. Conclusions: This work suggests the potential anti-leishmanial activity of the compounds and thus can be further in vitro and in vivo experimentally validated.

Idioma originalInglés
Número de artículo93
PublicaciónF1000Research
Volumen12
DOI
EstadoPublicada - 2023

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