Computational approaches for the design of novel anticancer compounds based on pyrazolo[3,4-d]pyrimidine derivatives as trap1 inhibitor

dc.contributor.authorAli, Amen
dc.contributor.authorAbdellattif, Magda H
dc.contributor.authorShahbaaz, Mohd
dc.date.accessioned2021-11-23T11:52:39Z
dc.date.available2021-11-23T11:52:39Z
dc.date.issued2021
dc.description.abstractIn the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R2 = 0.96 and Q2 = 0.57. Leave one out (LOO) cross-validation (R2 CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors.en_US
dc.identifier.citationAli, A. et al. (2021). Computational approaches for the design of novel anticancer compounds based on pyrazolo[3,4-d]pyrimidine derivatives as trap1 inhibitor. Molecules, 26(18),5482. https:// doi.org/10.3390/molecules26195932en_US
dc.identifier.issn1420-3049
dc.identifier.urihttps:// doi.org/10.3390/molecules26195932
dc.identifier.urihttp://hdl.handle.net/10566/7036
dc.language.isoenen_US
dc.publisherMPDIen_US
dc.subjectTRAP1 kinaseen_US
dc.subjectVirtual screeningen_US
dc.subjectMolecular dynamics simulationsen_US
dc.subjectPharmacophore modelingen_US
dc.subjectTRAP1 inhibitorsen_US
dc.titleComputational approaches for the design of novel anticancer compounds based on pyrazolo[3,4-d]pyrimidine derivatives as trap1 inhibitoren_US
dc.typeArticleen_US

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