Insights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSAR

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dc.contributor.authorQuesada-Romero, Luisa
dc.contributor.authorMena-Ulecia, Karel
dc.contributor.authorTiznado, William
dc.contributor.authorCaballero, Julio
dc.date.accessioned2023-06-08T14:52:18Z
dc.date.available2023-06-08T14:52:18Z
dc.date.issued2014-07
dc.descriptionIndexación: Scopus.es
dc.description.abstractMany protein kinase (PK) inhibitors have been reported in recent years, but only a few have been approved for clinical use. The understanding of the available molecular information using computational tools is an alternative to contribute to this process. With this in mind, we studied the binding modes of 77 maleimide derivates inside the PK glycogen synthase kinase 3 beta (GSK3b) using docking experiments. We found that the orientations that these compounds adopt inside GSK3b binding site prioritize the formation of hydrogen bond (HB) interactions between the maleimide group and the residues at the hinge region (residues Val135 and Asp133), and adopt propeller-like conformations (where the maleimide is the propeller axis and the heterocyclic substituents are two slanted blades). In addition, quantitative structure–activity relationship (QSAR) models using CoMSIA methodology were constructed to explain the trend of the GSK3b inhibitory activities for the studied compounds. We found a model to explain the structure–activity relationship of non-cyclic maleimide (NCM) derivatives (54 compounds). The best CoMSIA model (training set included 44 compounds) included steric, hydrophobic, and HB donor fields and had a good Q2 value of 0.539. It also predicted adequately the most active compounds contained in the test set. Furthermore, the analysis of the plots of the steric CoMSIA field describes the elements involved in the differential potency of the inhibitors that can be considered for the selection of suitable inhibitors.es
dc.description.urihttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102212
dc.identifier.citationPLoS ONE. Volume 9, Issue 7. 10 July 2014. Article number e102212es
dc.identifier.doiDOI: 10.1371/journal.pone.0102212
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/50477
dc.language.isoenes
dc.publisherPublic Library of Sciencees
dc.rights.licenseAtribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectProtein Kinaseses
dc.subjectCrystal Structurees
dc.subjectHeterocyclic Compoundses
dc.subjectLysinees
dc.subjectDihedral Angles
dc.subjectHeterocyclic Compounds
dc.subjectOvarian Cancer
dc.subjectPancreatic Cancer
dc.subjectPhosphorylation
dc.titleInsights into the interactions between maleimide derivates and GSK3β combining molecular docking and QSARes
dc.typeArtículoes
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