Toxicity and Anti-promastigote Activity of Benzoxazinoid Analogs Against and .

Journal: Advanced pharmaceutical bulletin
Published Date:

Abstract

Here, we aim to evaluate the antileishmanial activity of compounds with a benzoxazinoid (BX) skeleton, previously synthesized by our group, against and promastigotes. Anti-promastigote activity, as well as cytotoxicity, were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assays. The selectivity index (SI) for each compound was calculated using a ratio of the cytotoxicity of compounds and the geometric mean (GM) of antileishmanial concentrations to each species tested. The comparisons between groups were carried out using a t test or analysis of variance (one-way ANOVA). A P value of less than 0.05 was considered significant. All the compounds tested were active, with IC falling between 92±6.19 µg/mL and 238±6.57 µg/mL for L. braziliensis, and 89±6.43 µg/mL and 188±3.58 µg/mL against . Bex2, Bex3, Pyr1, Pyr2, and Pyr4 were compounds that showed activity similar to the drug Glucantime®, exhibited low cytotoxicity against splenic hamster cells (CC50 raging between >400 and 105.7±2.26 µg/mL) and had favorable selectivity indices (SI 1.12 to 3.96). The analogs in question are promising prototypes for the pharmaceutical development of novel, safer and more effective leishmanicidal agents.

Authors

  • Gilberto de Sousa
    Laboratório de Parasitologia e Doenças Parasitárias, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.
  • William Gustavo Lima
    Laboratório de Microbiologia Médica, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.
  • Flávio José Dos Santos
    Laboratório de Farmacognosia/Química de Produtos Naturais, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.
  • Francisco A Macías
    Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cadiz, Puerto Real (Cádiz), Spain.
  • José María González Molinillo
    Allelopathy Group, Department of Organic Chemistry, Institute of Biomolecules (INBIO), Campus CEIA3, School of Science, University of Cadiz, Puerto Real (Cádiz), Spain.
  • Rafael Gonçalves Teixeira-Neto
    Laboratório de Parasitologia e Doenças Parasitárias, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.
  • João Máximo de Siqueira
    Laboratório de Farmacognosia/Química de Produtos Naturais, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.
  • Eduardo Sérgio da Silva
    Laboratório de Parasitologia e Doenças Parasitárias, Campus Centro-Oeste Dona Lindu, Universidade Federal de São João Del-Rei (UFSJ), Divinopolis, MG, Brazil.

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