Title of article :
Toxicity and Anti-promastigote Activity of Benzoxazinoid Analogs Against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) infantum
Author/Authors :
de Sousa, Gilberto Laboratório de Parasitologia e Doenças Parasitárias - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil , Gustavo Lima, William Laboratório de Microbiologia Médica - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil , dos Santos, Flávio José Laboratório de Farmacognosia/Química de Produtos Naturais - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil , Macías, Francisco A. Allelopathy Group - Department of Organic Chemistry - Institute of Biomolecules (INBIO) - Campus CEIA3 - School of Science - University of Cadiz - Puerto Real (Cádiz), Spain , González Molinillo, José María Allelopathy Group - Department of Organic Chemistry - Institute of Biomolecules (INBIO) - Campus CEIA3 - School of Science - University of Cadiz - Puerto Real (Cádiz), Spain , Teixeira-Neto, Rafael Gonçalves Laboratório de Parasitologia e Doenças Parasitárias - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil , de Siqueira, João Máximo Laboratório de Farmacognosia/Química de Produtos Naturais - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil , da Silva, Eduardo Sérgio Laboratório de Parasitologia e Doenças Parasitárias - Campus Centro-Oeste Dona Lindu - Universidade Federal de São João Del-Rei (UFSJ) - Divinopolis - MG, Brazil
Abstract :
Purpose: Here, we aim to evaluate the antileishmanial activity of compounds with a
benzoxazinoid (BX) skeleton, previously synthesized by our group, against Leishmania (Viannia)
braziliensis and Leishmania (Leishmania) infantum promastigotes.
Methods: 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.
Results: All the compounds tested were active, with IC50 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 L.
infantum. 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).
Conclusion: The analogs in question are promising prototypes for the pharmaceutical
development of novel, safer and more effective leishmanicidal agents.
Keywords :
Benzoxazinone core , Leishmanicidal agents , Neglected disease , Pharmacology , Pyridoxazinone core , Splenic hamster cells
Journal title :
Advanced Pharmaceutical Bulletin
