Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i>
Chagas disease and leishmaniasis are neglected tropical diseases caused by kinetoplastid parasites of <i>Trypanosoma</i> and <i>Leishmania</i> genera that affect poor and remote populations in developing countries. These parasites share similar complex life cycles and modes o...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/657 |
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| author | Luis Cartuche Ines Sifaoui Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Desirée San Nicolás-Hernández Jacob Lorenzo-Morales José E. Piñero Ana R. Díaz-Marrero José J. Fernández |
| author_facet | Luis Cartuche Ines Sifaoui Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Desirée San Nicolás-Hernández Jacob Lorenzo-Morales José E. Piñero Ana R. Díaz-Marrero José J. Fernández |
| author_sort | Luis Cartuche |
| collection | DOAJ |
| description | Chagas disease and leishmaniasis are neglected tropical diseases caused by kinetoplastid parasites of <i>Trypanosoma</i> and <i>Leishmania</i> genera that affect poor and remote populations in developing countries. These parasites share similar complex life cycles and modes of infection. It has been demonstrated that the particular group of phosphorylating enzymes, protein kinases (PKs), are essential for the infective mechanisms and for parasite survival. The natural indolocarbazole staurosporine (STS, <b>1</b>) has been extensively used as a PKC inhibitor and its antiparasitic effects described. In this research, we analyze the antikinetoplastid activities of three indolocarbazole (ICZs) alkaloids of the family of staurosporine STS, <b>2</b>–<b>4</b>, and the commercial ICZs rebeccamycin (<b>5</b>), K252a (<b>6</b>), K252b (<b>7</b>), K252c (<b>8</b>), and arcyriaflavin A (<b>9</b>) in order to establish a plausive approach to the mode of action and to provide a preliminary qualitative structure–activity analysis. The most active compound was 7-oxostaurosporine (7OSTS, <b>2</b>) that showed IC<sub>50</sub> values of 3.58 ± 1.10; 0.56 ± 0.06 and 1.58 ± 0.52 µM against <i>L. amazonensis; L. donovani</i> and <i>T. cruzi,</i> and a Selectivity Index (CC<sub>50</sub>/IC<sub>50</sub>) of 52 against amastigotes of <i>L. amazonensis</i> compared to the J774A.1 cell line of mouse macrophages. |
| first_indexed | 2024-03-10T20:15:16Z |
| format | Article |
| id | doaj.art-3dbcd2705bb64871b77d5091bbc7b506 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:15:16Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-3dbcd2705bb64871b77d5091bbc7b5062023-11-19T22:38:20ZengMDPI AGBiomolecules2218-273X2020-04-0110465710.3390/biom10040657Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i>Luis Cartuche0Ines Sifaoui1Atteneri López-Arencibia2Carlos J. Bethencourt-Estrella3Desirée San Nicolás-Hernández4Jacob Lorenzo-Morales5José E. Piñero6Ana R. Díaz-Marrero7José J. Fernández8Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Avda. Astrofísico F. Sánchez s/n, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Tenerife, SpainInstituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez 2, 38206 La Laguna, Tenerife, SpainChagas disease and leishmaniasis are neglected tropical diseases caused by kinetoplastid parasites of <i>Trypanosoma</i> and <i>Leishmania</i> genera that affect poor and remote populations in developing countries. These parasites share similar complex life cycles and modes of infection. It has been demonstrated that the particular group of phosphorylating enzymes, protein kinases (PKs), are essential for the infective mechanisms and for parasite survival. The natural indolocarbazole staurosporine (STS, <b>1</b>) has been extensively used as a PKC inhibitor and its antiparasitic effects described. In this research, we analyze the antikinetoplastid activities of three indolocarbazole (ICZs) alkaloids of the family of staurosporine STS, <b>2</b>–<b>4</b>, and the commercial ICZs rebeccamycin (<b>5</b>), K252a (<b>6</b>), K252b (<b>7</b>), K252c (<b>8</b>), and arcyriaflavin A (<b>9</b>) in order to establish a plausive approach to the mode of action and to provide a preliminary qualitative structure–activity analysis. The most active compound was 7-oxostaurosporine (7OSTS, <b>2</b>) that showed IC<sub>50</sub> values of 3.58 ± 1.10; 0.56 ± 0.06 and 1.58 ± 0.52 µM against <i>L. amazonensis; L. donovani</i> and <i>T. cruzi,</i> and a Selectivity Index (CC<sub>50</sub>/IC<sub>50</sub>) of 52 against amastigotes of <i>L. amazonensis</i> compared to the J774A.1 cell line of mouse macrophages.https://www.mdpi.com/2218-273X/10/4/657Indolocarbazolekinetoplastid<i>Streptomyces</i>leishmanicidaltrypanocidal |
| spellingShingle | Luis Cartuche Ines Sifaoui Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Desirée San Nicolás-Hernández Jacob Lorenzo-Morales José E. Piñero Ana R. Díaz-Marrero José J. Fernández Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> Biomolecules Indolocarbazole kinetoplastid <i>Streptomyces</i> leishmanicidal trypanocidal |
| title | Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> |
| title_full | Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> |
| title_fullStr | Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> |
| title_full_unstemmed | Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> |
| title_short | Antikinetoplastid Activity of Indolocarbazoles from <i>Streptomyces sanyensis</i> |
| title_sort | antikinetoplastid activity of indolocarbazoles from i streptomyces sanyensis i |
| topic | Indolocarbazole kinetoplastid <i>Streptomyces</i> leishmanicidal trypanocidal |
| url | https://www.mdpi.com/2218-273X/10/4/657 |
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