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Nitro-Heterocyclic compounds induce apoptosis-like effects in promastigotes. | LitMetric
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 : 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-CH, BSF-H, BSF-NO, BSF-CH 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 : EC of amphotericin B and BSF-CH were 0.50 (M and 0.39 (M respective. Other nitro-heterocyclic compounds presented EC higher than amphotericin B. All compounds showed greater AV- and PI-positive expression than amphotericin B at 100 (M, except BSF-NO. TEM showed complete nuclear disfigurement with 100 (M of BSF-NO, 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-CH, 25 (M of BSF-H, 6.25 (M BSF-CH and 6.25 (M of BSF-Cl.Conclusions : Nitro-heterocyclic compounds have shown activity against promastigotes of at lower concentrations. However, improvement of compound scaffolds are needed to assist the elucidation of the mechanism of action and to achieve greater activity.
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