Next Article in Journal
Comprehensive Characterization of Lignans from Forsythia viridissima by UHPLC-ESI-QTOF-MS, and Their NO Inhibitory Effects on RAW 264.7 Cells
Next Article in Special Issue
Thiol-ene "Click" Synthesis and Pharmacological Evaluation of C-Glycoside sp2-Iminosugar Glycolipids
Previous Article in Journal
Analysis of Chemical Composition and Assessment of Cytotoxic, Antimicrobial, and Antioxidant Activities of the Essential Oil of Meriandra dianthera Growing in Saudi Arabia
Previous Article in Special Issue
Synthesis, Crystal Structure, and Biological Evaluation of Fused Thiazolo[3,2-a]Pyrimidines as New Acetylcholinesterase Inhibitors
Open AccessArticle

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

1
Departamento de Química, Universidad Autónoma Metropolitana-Iztapalapa, San Rafael Atlixco 186, Col. Vicentina, C.P. 09340, Iztapalapa, Mexico City, Mexico
2
Departamento de Polímeros, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, Coyoacán, Mexico City C.P. 04510, Mexico
3
Laboratorio de Fisicoquímica y Reactividad de Superficies, Instituto de Investigaciones en Materiales, Universidad Nacional Autónoma de México, Circuito Exterior S/N, Ciudad Universitaria, Coyoacán, Mexico City C.P. 04510, Mexico
4
Departamento de Alimentos, Centro Interdisciplinario del Noreste, Universidad de Guanajuato, Tierra Blanca, Guanajuato C.P. 37975, Mexico
5
División de Medicina Genómica, Centro Médico Nacional 20 de Noviembre, ISSSTE, Félix Cuevas 540, Col. Del Valle Sur, Benito Juárez, Mexico City C.P. 03100, Mexico
*
Authors to whom correspondence should be addressed.
Academic Editor: David Díez
Molecules 2019, 24(14), 2648; https://doi.org/10.3390/molecules24142648
Received: 17 June 2019 / Revised: 8 July 2019 / Accepted: 18 July 2019 / Published: 22 July 2019
(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds)
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. View Full-Text
Keywords: pyrrolo[3,4-b]pyridin-5-ones; paclitaxel; αβ-tubulin; cervical cancer; SiHa; HeLa; Caski; molecular docking; QSAR; pharmacophore model pyrrolo[3,4-b]pyridin-5-ones; paclitaxel; αβ-tubulin; cervical cancer; SiHa; HeLa; Caski; molecular docking; QSAR; pharmacophore model
Show Figures

Graphical abstract

MDPI and ACS Style

Segura-Olvera, D.; García-González, A.N.; Morales-Salazar, I.; Islas-Jácome, A.; Rojas-Aguirre, Y.; Ibarra, I.A.; Díaz-Cervantes, E.; Alcaraz-Estrada, S.L.; González-Zamora, E. 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. Molecules 2019, 24, 2648.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop