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

• Autor(a) principal: Krombauer,Gabriela Camila
• Data de Publicação: 2022
• Outros Autores: Guedes,Karla de Sena, Banfi,Felipe Fingir, Nunes,Renata Rachide, Fonseca,Amanda Luisa da, Siqueira,Ezequias Pessoa de, Bellei,Jéssica Côrrea Bezerra, Scopel,Kézia Katiani Gorza, Varotti,Fernando de Pilla, Sanchez,Bruno Antônio Marinho
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Revista da Sociedade Brasileira de Medicina Tropical
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822022000100333
• topic: Malaria; Chemotherapy; Antimalarial; Docking

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.