Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes
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...
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| Format: | Article |
| Language: | English |
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SciELO
2019-03-01
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| Series: | Journal of Venomous Animals and Toxins including Tropical Diseases |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100303&lng=en&tlng=en |
| _version_ | 1818982042164002816 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Daiane Barros Dias Mendonça |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T17:40:55Z |
| format | Article |
| id | doaj.art-72ada59c8dec449b941369d62da8497a |
| institution | Directory Open Access Journal |
| issn | 1678-9199 |
| language | English |
| last_indexed | 2024-12-20T17:40:55Z |
| publishDate | 2019-03-01 |
| publisher | SciELO |
| record_format | Article |
| series | Journal of Venomous Animals and Toxins including Tropical Diseases |
| spelling | doaj.art-72ada59c8dec449b941369d62da8497a2022-12-21T19:31:07ZengSciELOJournal of Venomous Animals and Toxins including Tropical Diseases1678-91992019-03-0125010.1590/1678-9199-jvatitd-1444-18S1678-91992019000100303Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotesDaiane Barros Dias MendonçaRenata Ellen Costa SilvaFanny Palace-BerlCleusa FH TakakuraSandra Regina C SoaresLucia Maria Almeida BrazLeoberto Costa TavaresJose Angelo Lauletta LindosoAbstract 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100303&lng=en&tlng=enLeishmaniasis treatmentNitro-heterocyclic compoundsLeishmania (L.) amazonensis |
| spellingShingle | 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 Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes Journal of Venomous Animals and Toxins including Tropical Diseases Leishmaniasis treatment Nitro-heterocyclic compounds Leishmania (L.) amazonensis |
| title | Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes |
| title_full | Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes |
| title_fullStr | Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes |
| title_full_unstemmed | Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes |
| title_short | Nitro-Heterocyclic compounds induce apoptosis-like effects in Leishmania (L). amazonensis promastigotes |
| title_sort | nitro heterocyclic compounds induce apoptosis like effects in leishmania l amazonensis promastigotes |
| topic | Leishmaniasis treatment Nitro-heterocyclic compounds Leishmania (L.) amazonensis |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100303&lng=en&tlng=en |
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