Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer
Prostaglandin A<sub>2</sub>-AcMe (<b>1</b>) and Prostaglandin A<sub>2</sub> (<b>2</b>) were isolated from the octocoral <i>Plexaura</i> <i>homomalla</i> and three semisynthetic derivatives (<b>3</b>−<b&g...
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MDPI AG
2020-02-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/3/141 |
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| author | Diana Ximena Hurtado Fabio A. Castellanos Ericsson Coy-Barrera Edisson Tello |
| author_facet | Diana Ximena Hurtado Fabio A. Castellanos Ericsson Coy-Barrera Edisson Tello |
| author_sort | Diana Ximena Hurtado |
| collection | DOAJ |
| description | Prostaglandin A<sub>2</sub>-AcMe (<b>1</b>) and Prostaglandin A<sub>2</sub> (<b>2</b>) were isolated from the octocoral <i>Plexaura</i> <i>homomalla</i> and three semisynthetic derivatives (<b>3</b>−<b>5</b>) were then obtained using a reduction protocol. All compounds were identified through one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) experiments. Additionally, evaluation of in vitro cytotoxic activity against the breast (MDA-MB-213) and lung (A549) cancer cell lines, in combination with enzymatic activity and molecular docking studies with the enzymes p38α-kinase, Src-kinase, and topoisomerase IIα, were carried out for compounds <b>1</b>−<b>5</b> in order to explore their potential as inhibitors of cancer-related molecular targets. Results showed that prostaglandin A<sub>2</sub> (<b>2</b>) was the most potent compound with an IC<sub>50</sub> of 16.46 and 25.20 μg/mL against MDA-MB-213 and A549 cell lines, respectively. In addition, this compound also inhibited p38α-kinase in 49% and Src-kinase in 59% at 2.5 μM, whereas topoisomerase IIα was inhibited in 64% at 10 μM. Enzymatic activity was found to be consistent with molecular docking simulations, since compound <b>2</b> also showed the lowest docking scores against the topoisomerase IIα and Src-kinase (−8.7 and −8.9 kcal/mol, respectively). Thus, molecular docking led to establish some insights into the predicted binding modes. Results suggest that prostaglandin 2 can be considered as a potential lead for development inhibitors against some enzymes present in cancer processes. |
| first_indexed | 2024-04-11T12:59:53Z |
| format | Article |
| id | doaj.art-d7a08971dfef465f98b5f382b1b8bee3 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T12:59:53Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-d7a08971dfef465f98b5f382b1b8bee32022-12-22T04:22:59ZengMDPI AGMarine Drugs1660-33972020-02-0118314110.3390/md18030141md18030141Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of CancerDiana Ximena Hurtado0Fabio A. Castellanos1Ericsson Coy-Barrera2Edisson Tello3Bioprospecting Research Group, Faculty of Engineering, Maestría en diseño y Gestión de Procesos, Universidad de La Sabana, Campus del Puente del Común, Km. 7, Autopista Norte de Bogotá, Chía, Cundinamarca 250001, ColombiaBioprospecting Research Group, Faculty of Engineering, Maestría en diseño y Gestión de Procesos, Universidad de La Sabana, Campus del Puente del Común, Km. 7, Autopista Norte de Bogotá, Chía, Cundinamarca 250001, ColombiaBioorganic Chemistry Laboratory, Facultad de Ciencias Básicas y Aplicadas, Universidad Militar Nueva Granada, Cajicá 250247, ColombiaBioprospecting Research Group, Faculty of Engineering, Maestría en diseño y Gestión de Procesos, Universidad de La Sabana, Campus del Puente del Común, Km. 7, Autopista Norte de Bogotá, Chía, Cundinamarca 250001, ColombiaProstaglandin A<sub>2</sub>-AcMe (<b>1</b>) and Prostaglandin A<sub>2</sub> (<b>2</b>) were isolated from the octocoral <i>Plexaura</i> <i>homomalla</i> and three semisynthetic derivatives (<b>3</b>−<b>5</b>) were then obtained using a reduction protocol. All compounds were identified through one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) experiments. Additionally, evaluation of in vitro cytotoxic activity against the breast (MDA-MB-213) and lung (A549) cancer cell lines, in combination with enzymatic activity and molecular docking studies with the enzymes p38α-kinase, Src-kinase, and topoisomerase IIα, were carried out for compounds <b>1</b>−<b>5</b> in order to explore their potential as inhibitors of cancer-related molecular targets. Results showed that prostaglandin A<sub>2</sub> (<b>2</b>) was the most potent compound with an IC<sub>50</sub> of 16.46 and 25.20 μg/mL against MDA-MB-213 and A549 cell lines, respectively. In addition, this compound also inhibited p38α-kinase in 49% and Src-kinase in 59% at 2.5 μM, whereas topoisomerase IIα was inhibited in 64% at 10 μM. Enzymatic activity was found to be consistent with molecular docking simulations, since compound <b>2</b> also showed the lowest docking scores against the topoisomerase IIα and Src-kinase (−8.7 and −8.9 kcal/mol, respectively). Thus, molecular docking led to establish some insights into the predicted binding modes. Results suggest that prostaglandin 2 can be considered as a potential lead for development inhibitors against some enzymes present in cancer processes.https://www.mdpi.com/1660-3397/18/3/141octocoralsprostaglandinmolecular dockingbreast and lung cancerp38-kinasesrc-kinasetopoisomerase iiα |
| spellingShingle | Diana Ximena Hurtado Fabio A. Castellanos Ericsson Coy-Barrera Edisson Tello Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer Marine Drugs octocorals prostaglandin molecular docking breast and lung cancer p38-kinase src-kinase topoisomerase iiα |
| title | Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer |
| title_full | Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer |
| title_fullStr | Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer |
| title_full_unstemmed | Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer |
| title_short | Prostaglandins Isolated from the Octocoral <i>Plexaura homomalla</i>: In Silico and In Vitro Studies Against Different Enzymes of Cancer |
| title_sort | prostaglandins isolated from the octocoral i plexaura homomalla i in silico and in vitro studies against different enzymes of cancer |
| topic | octocorals prostaglandin molecular docking breast and lung cancer p38-kinase src-kinase topoisomerase iiα |
| url | https://www.mdpi.com/1660-3397/18/3/141 |
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