Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes
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-het...
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| Published in: | The journal of venomous animals and toxins including tropical diseases Vol. 25; p. e144418 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Brazil
Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP
2019
Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP/UNESP) SciELO |
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| Online Access: | Get full text |
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| Summary: | 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.
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-C
H
, 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.
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-C
H
, 25 (M of BSF-H, 6.25 (M BSF-CH
and 6.25 (M of BSF-Cl.
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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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing interests: The authors declare that there are no conflicts of interest. Authors' contributions: DBDM designed and performed all experiments and wrote the manuscript. RECS take part in the experiments related to cytometry. FPB was responsible for synthesis of compounds and corrected the manuscript. CFHT took part in the experiments related to transmission electron microscopy. SRCS helped in all experiments. LMAB helped to write the manuscript. LCT was responsible for compounds and corrected the manuscript. JALL designed the experiments, and wrote and corrected the manuscript. |
| ISSN: | 1678-9199 1678-9199 |
| DOI: | 10.1590/1678-9199-JVATITD-1444-18 |