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dc.contributor.authorMéndez Luna, David
dc.contributor.authorGómez Vidal, José Antonio
dc.identifier.citationMéndez-Luna, D.; Morelos-Garnica, L.A.; García-Vázquez, J.B.; Bello, M.; Padilla-Martínez, I.I.; Fragoso-Vázquez, M.J.; Dueñas González, A.; De Pedro, N.; Gómez-Vidal, J.A.; Mendoza-Figueroa, H.L.; et al. Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells. Pharmaceuticals 2021, 14, 49.
dc.description.abstractThe implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2- yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.es_ES
dc.description.sponsorshipCONACYT (Grants: CB-254600, APN-782 and SEP-CONACYT-ANUIES-ECOS Francia: 296636)es_ES
dc.description.sponsorshipInstituto Politécnico Nacional (Grant: Proyectos Insignia IPN-2015)es_ES
dc.rightsAtribución 3.0 España*
dc.subjectMolecular dynamics simulationses_ES
dc.subjectSuzuki–Miyaura cross-couplinges_ES
dc.subjectTetrahydroquinoline scaffoldes_ES
dc.titleModifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cellses_ES

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Atribución 3.0 España
Except where otherwise noted, this item's license is described as Atribución 3.0 España