In vitro and in silico assessment of new beta amino ketones with antiplasmodial activity

• Published in: Revista da Sociedade Brasileira de Medicina Tropical
• Main Authors: Gabriela Camila Krombauer, Karla de Sena Guedes, Felipe Fingir Banfi, Renata Rachide Nunes, Amanda Luisa da Fonseca, Ezequias Pessoa de Siqueira, Jéssica Côrrea Bezerra Bellei, Kézia Katiani Gorza Scopel, Fernando de Pilla Varotti, Bruno Antônio Marinho Sanchez
• Format: Article in Journal/Newspaper
• Language: English
• Published: Sociedade Brasileira de Medicina Tropical (SBMT) 2022
• Subjects: Malaria; Chemotherapy; Antimalarial; Docking; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.1590/0037-8682-0590-2022; https://doaj.org/article/354adf833dd84bf99483d14284f13ab9

ABSTRACT Background: Based on the current need for new drugs against malaria, our study evaluated eight beta amino ketones in silico and in vitro for potential antimalarial activity. Methods: Using the Brazilian Malaria Molecular Targets (BraMMT) and OCTOPUS® software programs, the pattern of interactions of beta-amino ketones was described against different proteins of P. falciparum and screened to evaluate their physicochemical properties. The in vitro antiplasmodial activities of the compounds were evaluated using a SYBR Green-based assay. In parallel, in vitro cytotoxic data were obtained using the MTT assay. Results: Among the eight compounds, compound 1 was the most active and selective against P. falciparum (IC50 = 0.98 µM; SI > 60). Six targets were identified in BraMMT that interact with compounds exhibiting a stronger binding energy than the crystallographic ligand: P. falciparum triophosphate phosphoglycolate complex (1LYX), P. falciparum reductase (2OK8), PfPK7 (2PML), P. falciparum glutaredoxin (4N0Z), PfATP6, and PfHT. Conclusions: The physicochemical properties of compound 1 were compatible with the set of criteria established by the Lipinski rule and demonstrated its potential as a drug prototype for antiplasmodial activity.