In vitro and in silico assessment of new beta amino ketones with antiplasmodial activity
Rev. Soc. Bras. Med. Trop
; 55: e0590, 2022. tab, graf
Article
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LILACS-Express
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| ID: biblio-1407001
Biblioteca responsável:
BR1.1
ABSTRACT
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.
Texto completo:
1
Índice:
LILACS
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Rev. Soc. Bras. Med. Trop
Assunto da revista:
MEDICINA TROPICAL
Ano de publicação:
2022
Tipo de documento:
Article
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Project document