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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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