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Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines
A series of 12 polysubstituted pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot cascade process (Ugi–3CR/aza Diels-Alder/N-acylation/decarboxylation/dehydration) and studied in vitro using human epithelial cervical carcinoma SiHa, HeLa, and CaSki cell line cultures. Three compounds of the...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680468/ https://www.ncbi.nlm.nih.gov/pubmed/31336585 http://dx.doi.org/10.3390/molecules24142648 |
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author | Segura-Olvera, Daniel García-González, Ailyn N. Morales-Salazar, Ivette Islas-Jácome, Alejandro Rojas-Aguirre, Yareli Ibarra, Ilich A. Díaz-Cervantes, Erik Alcaraz-Estrada, Sofía Lizeth González-Zamora, Eduardo |
author_facet | Segura-Olvera, Daniel García-González, Ailyn N. Morales-Salazar, Ivette Islas-Jácome, Alejandro Rojas-Aguirre, Yareli Ibarra, Ilich A. Díaz-Cervantes, Erik Alcaraz-Estrada, Sofía Lizeth González-Zamora, Eduardo |
author_sort | Segura-Olvera, Daniel |
collection | PubMed |
description | A series of 12 polysubstituted pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot cascade process (Ugi–3CR/aza Diels-Alder/N-acylation/decarboxylation/dehydration) and studied in vitro using human epithelial cervical carcinoma SiHa, HeLa, and CaSki cell line cultures. Three compounds of the series exhibited significative cytotoxicity against the three cell lines, with HeLa being the most sensitive one. Then, based on these results, in silico studies by docking techniques were performed using Paclitaxel as a reference and αβ-tubulin as the selected biological target. Worth highlighting is that strong hydrophobic interactions were observed between the three active molecules and the reference drug Paclitaxel, to the αβ-tubulin. In consequence, it was determined that hydrophobic–aromatic moieties of bioactive compounds and Paclitaxel play a key role in making stronger interactions to the ligand–target complex. A quantitative structure activity relationship (QSAR) study revealed that the six membered rings are the most significant molecular frameworks, being present in all proposed models for the in vitro-studied cell lines. Finally, also from the docking interpretation, a ligand-based pharmacophore model is proposed in order to find further potential polyheterocyclic candidates to bind stronger to the αβ-tubulin. |
format | Online Article Text |
id | pubmed-6680468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66804682019-08-09 Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines Segura-Olvera, Daniel García-González, Ailyn N. Morales-Salazar, Ivette Islas-Jácome, Alejandro Rojas-Aguirre, Yareli Ibarra, Ilich A. Díaz-Cervantes, Erik Alcaraz-Estrada, Sofía Lizeth González-Zamora, Eduardo Molecules Article A series of 12 polysubstituted pyrrolo[3,4-b]pyridin-5-ones were synthesized via a one-pot cascade process (Ugi–3CR/aza Diels-Alder/N-acylation/decarboxylation/dehydration) and studied in vitro using human epithelial cervical carcinoma SiHa, HeLa, and CaSki cell line cultures. Three compounds of the series exhibited significative cytotoxicity against the three cell lines, with HeLa being the most sensitive one. Then, based on these results, in silico studies by docking techniques were performed using Paclitaxel as a reference and αβ-tubulin as the selected biological target. Worth highlighting is that strong hydrophobic interactions were observed between the three active molecules and the reference drug Paclitaxel, to the αβ-tubulin. In consequence, it was determined that hydrophobic–aromatic moieties of bioactive compounds and Paclitaxel play a key role in making stronger interactions to the ligand–target complex. A quantitative structure activity relationship (QSAR) study revealed that the six membered rings are the most significant molecular frameworks, being present in all proposed models for the in vitro-studied cell lines. Finally, also from the docking interpretation, a ligand-based pharmacophore model is proposed in order to find further potential polyheterocyclic candidates to bind stronger to the αβ-tubulin. MDPI 2019-07-22 /pmc/articles/PMC6680468/ /pubmed/31336585 http://dx.doi.org/10.3390/molecules24142648 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Segura-Olvera, Daniel García-González, Ailyn N. Morales-Salazar, Ivette Islas-Jácome, Alejandro Rojas-Aguirre, Yareli Ibarra, Ilich A. Díaz-Cervantes, Erik Alcaraz-Estrada, Sofía Lizeth González-Zamora, Eduardo Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title | Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title_full | Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title_fullStr | Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title_full_unstemmed | Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title_short | Synthesis of Pyrrolo[3,4-b]pyridin-5-ones via Multicomponent Reactions and In Vitro–In Silico Studies Against SiHa, HeLa, and CaSki Human Cervical Carcinoma Cell Lines |
title_sort | synthesis of pyrrolo[3,4-b]pyridin-5-ones via multicomponent reactions and in vitro–in silico studies against siha, hela, and caski human cervical carcinoma cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680468/ https://www.ncbi.nlm.nih.gov/pubmed/31336585 http://dx.doi.org/10.3390/molecules24142648 |
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