Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i>
The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the <i>Trypanosoma cruzi</i> CLB strain (DTU TcVI). The compounds were initially screened agai...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/5/705 |
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| author | Rocío Herráez Roberto Quesada Norma Dahdah Miguel Viñas Teresa Vinuesa |
| author_facet | Rocío Herráez Roberto Quesada Norma Dahdah Miguel Viñas Teresa Vinuesa |
| author_sort | Rocío Herráez |
| collection | DOAJ |
| description | The aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the <i>Trypanosoma cruzi</i> CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC<sub>50</sub> values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC<sub>50</sub>), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease. |
| first_indexed | 2024-03-10T11:30:10Z |
| format | Article |
| id | doaj.art-dd65907d794b4f5d8127112ba7a14ba1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:30:10Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-dd65907d794b4f5d8127112ba7a14ba12023-11-21T19:20:50ZengMDPI AGPharmaceutics1999-49232021-05-0113570510.3390/pharmaceutics13050705Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i>Rocío Herráez0Roberto Quesada1Norma Dahdah2Miguel Viñas3Teresa Vinuesa4Department of Pathology and Experimental Therapeutics, Medical School, University of Barcelona, 08021 Barcelona, SpainDepartamento de Química, Universidad de Burgos, 09001 Burgos, SpainDepartament de Ciències Fisiològiques, Medical School, University of Barcelona, 08907 Barcelona, SpainDepartment of Pathology and Experimental Therapeutics, Medical School, University of Barcelona, 08021 Barcelona, SpainDepartment of Pathology and Experimental Therapeutics, Medical School, University of Barcelona, 08021 Barcelona, SpainThe aim of this work was to explore new therapeutic options against Chagas disease by the in vitro analysis of the biocidal activities of several tambjamine and prodiginine derivatives, against the <i>Trypanosoma cruzi</i> CLB strain (DTU TcVI). The compounds were initially screened against epimastigotes. The five more active compounds were assayed in intracellular forms. The tambjamine MM3 and both synthetic and natural prodigiosins displayed the highest trypanocidal profiles, with IC<sub>50</sub> values of 4.52, 0.46, and 0.54 µM for epimastigotes and 1.9, 0.57, and 0.1 µM for trypomastigotes/amastigotes, respectively. Moreover, the combination treatment of these molecules with benznidazole showed no synergism. Finally, oxygen consumption inhibition determinations performed using high-resolution respirometry, revealed a potent effect of prodigiosin on parasite respiration (73% of inhibition at ½ IC<sub>50</sub>), suggesting that its mode of action involves the mitochondria. Moreover, its promising selectivity index (50) pointed out an interesting trypanocidal potential and highlighted the value of prodigiosin as a new candidate to fight Chagas disease.https://www.mdpi.com/1999-4923/13/5/705<i>Trypanosoma cruzi</i>tambjaminesprodigiosinobatoclaxanti-chagasic agentscytotoxicity |
| spellingShingle | Rocío Herráez Roberto Quesada Norma Dahdah Miguel Viñas Teresa Vinuesa Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> Pharmaceutics <i>Trypanosoma cruzi</i> tambjamines prodigiosin obatoclax anti-chagasic agents cytotoxicity |
| title | Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> |
| title_full | Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> |
| title_fullStr | Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> |
| title_full_unstemmed | Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> |
| title_short | Tambjamines and Prodiginines: Biocidal Activity against <i>Trypanosoma cruzi</i> |
| title_sort | tambjamines and prodiginines biocidal activity against i trypanosoma cruzi i |
| topic | <i>Trypanosoma cruzi</i> tambjamines prodigiosin obatoclax anti-chagasic agents cytotoxicity |
| url | https://www.mdpi.com/1999-4923/13/5/705 |
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