In silico, in vitro and in vivo evaluation of natural Bignoniaceous naphthoquinones in comparison with atovaquone targeting the selection of potential antimalarial candidates.

Autor: do Nascimento MFA; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil., Borgati TF; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil., de Souza LCR; Departamento de Inovação Tecnológica, Instituto de Ciências Biológicas, Universidade Federal de Minas, Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil., Tagliati CA; Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas, Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil., de Oliveira AB; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, MG 31.270-901, Brazil. Electronic address: bragalaide@gmail.com.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2020 Aug 15; Vol. 401, pp. 115074. Date of Electronic Publication: 2020 May 26.
DOI: 10.1016/j.taap.2020.115074
Abstrakt: The natural naphthoquinones lapachol, α- and β-lapachone are found in Bignoniaceous Brazilian plant species of the Tabebuia genus (synonym Handroanthus) and are recognized for diverse bioactivities, including as antimalarial. The aim of the present work was to perform in silico, in vitro and in vivo studies to evaluating the antimalarial potential of these three naphthoquinones in comparison with atovaquone, a synthetic antimalarial. The ADMET properties of these compounds were predicted in silico by the preADMET program. The in vitro toxicity assays were experimentally determined in immortalized and tumoral cells from different organs. In vivo acute oral toxicity was also evaluated for lapachol. Several favorable pharmacokinetics data were predicted although, as expected, high cytotoxicity was experimentally determined for β-lapachone. Lapachol was not cytotoxic or showed low cytotoxicity to all of the cells assayed (HepG2, A549, Neuro 2A, LLC-PK1, MRC-5), it was nontoxic in the acute oral test and disclosed the best parasite selectivity index in the in vitro assays against chloroquine resistant Plasmodium falciparum W2 strain. On the other hand, α- and β-lapachone were more potent than lapachol in the antiplasmodial assays but with low parasite selectivity due to their cytotoxicity. The diversity of data here reported disclosed lapachol as a promising candidate to antimalarial drug development.
Competing Interests: Declaration of Competing Interest All the authors declare to have no conflict of interests.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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