Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L) amazonensis promastigotes

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03/12/2019

Daiane Barros Dias Mendonça, Renata Ellen Costa Silva, Fanny Palace-Berl, Cleusa FH Takakura, Sandra Regina C Soares, Lucia Maria Almeida Braz, Leoberto Costa Tavares, Jose Angelo Lauletta Lindoso

Journal of Venomous Animals and Toxins including Tropical Diseases 2019;25:e144418
http://dx.doi.org/10.1590/1678-9199-jvatitd-1444-18 | © The Author(s). 2019
Received: May 3, 2018 | Accepted: November 30, 2018 | Published: March 11, 2019

ABSTRACT

Background

Three drugs – pentavalent antimonials, amphotericin B and pentamidine – are currently used for leishmaniasis treatment. They are administered for long periods, only parenterally, and have high cardiac, renal and hepatic toxicities. Therefore, the investigation of new compounds is required. Nitro-heterocyclic derivatives have been used as possible drug candidates to treat diseases caused by trypanosomatids.

Methods

Leishmania (L.) amazonensis promastigotes (MHO/BR/73/M2269), maintained in the Laboratório de Soroepidemiologia – Instituto de Medicina Tropical- USP, were exposed to five nitroheterocyclic derivatives, with differences at phenyl-ring position 4: BSF-C4H9, BSF-H, BSF-NO2, BSF-CH3 and BSF-Cl, for 48 hours. After analyzing viability (MTT assay), we evaluated cellular-morphology activity of compounds by transmission electron microscopy (TEM) and measurement of apoptosis (phosphatidylserine expression) by flow cytometry.

Results

EC50 of amphotericin B and BSF-CH3 were 0.50 (M and 0.39 (M respective. Other nitro-heterocyclic compounds presented EC50 higher than amphotericin B. All compounds showed greater AV- and PI-positive expression than amphotericin B at 100 (M, except BSF-NO2. TEM showed complete nuclear disfigurement with 100 (M of BSF-NO2, 25 and 6.25 (M of BSF-H, and 6.25 (M BSF-Cl; presence of vesicles within the flagellar pocket with 25 (M BSF-H; alteration of the kinetoplast with 25 (M BSF-C4H9, 25 (M of BSF-H, 6.25 (M BSF-CH3 and 6.25 (M of BSF-Cl.

Conclusions

Nitro-heterocyclic compounds have shown activity against promastigotes of L. amazonensis, at lower concentrations. However, improvement of compound scaffolds are needed to assist the elucidation of the mechanism of action and to achieve greater activity.

PubMed Central https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521708/

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KEYWORDS

Leishmaniasis treatment
Nitro-heterocyclic compounds
Leishmania (L.) amazonensis
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