Antiplasmodial activity of coumarins isolated from Polygala boliviensis : in vitro and in silico studies.

Autor:	da Silva DF; Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., de Souza JL; Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., da Costa DM; Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., Costa DB Jr; Departamento de Saúde, Laboratório de Modelagem Molecular, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., Moreira POL; Centro de Ciências da Saúde, Laboratório de Bioquímica Medicinal, Universidade Federal de São João Del-Rei, Divinópolis, Minas Gerais, Brazil., Fonseca ALD; Centro de Ciências da Saúde, Laboratório de Bioquímica Medicinal, Universidade Federal de São João Del-Rei, Divinópolis, Minas Gerais, Brazil., Varotti FP; Centro de Ciências da Saúde, Laboratório de Bioquímica Medicinal, Universidade Federal de São João Del-Rei, Divinópolis, Minas Gerais, Brazil., Cruz JN; Departamento de Ciências Biológicas e da Saúde, Laboratório de Modelagem e Química Computacional, Universidade Federal do Amapá, Macapá, Amapá, Brazil., Dos Santos CBR; Departamento de Ciências Biológicas e da Saúde, Laboratório de Modelagem e Química Computacional, Universidade Federal do Amapá, Macapá, Amapá, Brazil., Alves CQ; Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., Leite FHA; Departamento de Saúde, Laboratório de Modelagem Molecular, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil., Brandão HN; Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil.
Jazyk:	angličtina
Zdroj:	Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023; Vol. 41 (22), pp. 13383-13403. Date of Electronic Publication: 2023 Feb 06.
DOI:	10.1080/07391102.2023.2173295
Abstrakt:	Polygala boliviensis is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. Polygala spp. have different metabolites, especially coumarins. Studies indicate that coumarins have antimalarial potential, denoting the importance of researching new active compounds from plants, since the resistance of Plasmodium strains to conventional therapy has increased. The present study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of Plasmodium falciparum . Coumarins were isolated from P. boliviensis by open column chromatography and identified by Nuclear Magnetic Resonance Spectroscopy. A cytotoxicity assay was carried out using MTT test, and the in vitro antiplasmodial activity was evaluated using the W2 strain. The antiplasmodial activity results found were IC 50 =0.171 ± 0.016 for auraptene and 0.164 ± 0.012 for poligalen; the selectivity indexes were 78.71 and 609.76, respectively. Inverse virtual screening in the BRAMMT database by OCTOPUS 1.2 was applied to coumarins to find potential P. falciparum targets and showed higher affinity energy of auraptene for purine nucleoside phosphorylase (PfPNP) and of poligalen for dihydroorotate dehydrogenase (PfDHODH). Molecular Dynamics studies (MD and MM-GBSA) approach were applied to calculate binding energies against selected P. falciparum targets and showed that all coumarins were stable at the binding site during simulations. Furthermore, energies were favorable for complexation. This is the first report of auraptene in P. boliviensis species and of in vitro antiplasmodial activity of auraptene and poligalen. In silico studies indicated that the mechanism of action of coumarins is the inhibition of PfPNP and PfDHODH.Communicated by Ramaswamy H. Sarma.
Databáze:	MEDLINE
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