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

Autor:	Barazorda-Ccahuana HL; Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, Peru., Goyzueta-Mamani LD; Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, Peru.; Sustainable Innovative Biomaterials Department, Le Qara Research Center, Arequipa, Peru., Candia Puma MA; Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, Peru.; Universidad Católica de Santa María, Facultad de Ciencias Farmacéuticas, Bioquímicas y Biotecnológicas, Arequipa, Peru., Simões de Freitas C; Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, Brazil., de Sousa Vieria Tavares G; Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, Brazil., Pagliara Lage D; Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, Brazil., Ferraz Coelho EA; Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Belo Horizonte, Minas Gerais, Brazil.; Universidade Federal de Minas Gerais, Departamento de Patologia Clínica, COLTEC, Belo Horizonte, Minas Gerais, Brazil., Chávez-Fumagalli MA; Computational Biology and Chemistry Research Group, Vicerrectorado de Investigación, Universidad Catolica de Santa Maria de Arequipa, Arequipa, Peru.
Jazyk:	angličtina
Zdroj:	F1000Research [F1000Res] 2023 Jul 13; Vol. 12, pp. 93. Date of Electronic Publication: 2023 Jul 13 (Print Publication: 2023).
DOI:	10.12688/f1000research.129943.3
Abstrakt:	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. Competing Interests: No competing interests were disclosed. (Copyright: © 2023 Barazorda-Ccahuana HL et al.)
Databáze:	MEDLINE
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