In vitro and in silico assessment of new beta amino ketones with antiplasmodial activity
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 intera...
Published in: | Revista da Sociedade Brasileira de Medicina Tropical |
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Main Authors: | , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Sociedade Brasileira de Medicina Tropical (SBMT)
2022
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Subjects: | |
Online Access: | https://doi.org/10.1590/0037-8682-0590-2022 https://doaj.org/article/354adf833dd84bf99483d14284f13ab9 |
Summary: | 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. |
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