In silico binding mechanism prediction of benzimidazole based corticotropin releasing factor-1 receptor antagonists by quantitative structure activity relationship, molecular docking and pharmacokinetic parameters calculation

dc.contributor.authorKumar, N.
dc.contributor.authorMishra, S.S.
dc.contributor.authorSharma, C.S.
dc.contributor.authorSingh, H.P.
dc.contributor.authorKalra, S.
dc.date.accessioned2018-07-14T01:18:51Z
dc.date.accessioned2024-08-14T07:41:17Z
dc.date.available2018-07-14T01:18:51Z
dc.date.available2024-08-14T07:41:17Z
dc.date.issued2018
dc.description.abstractDespite the various research efforts toward the treatment of stress-related disorders, the drug has not yet launched last 20?years. Corticotropin releasing factor-1 receptor antagonists have been point of great interest in stress-related disorders. In the present study, we have selected benzazole scaffold-based compounds as corticotropin releasing factor-1 antagonists and performed 2D and 3D QSAR studies to identify the structural features to elucidating the binding mechanism prediction. The best 2D QSAR model was obtained through multiple linear regression method with r2 value of.7390, q2 value of.5136 and pred_r2 (predicted square correlation coefficient) value of.88. The contribution of 2D descriptor, T_2_C_1 was 60% (negative contribution) and 4pathClusterCount was 40.24% (positive contribution) in enhancing the activity. Also 3D QSAR model was statistically significant with q2 value of.9419 and q2_se (standard error of internal validation) value of.19. Statistical parameters results prove the robustness and significance of both models. Further, molecular docking and pharmacokinetic analysis was performed to explore the scope of investigation. Docking results revealed that the all benzazole compounds show hydrogen bonding with residue Asn283 and having same hydrophobic pocket (Phe286, Leu213, Ile290, Leu287, Phe207, Arg165, Leu323, Tyr327, Phe284, and Met206). Compound B14 has higher activity compare to reference molecules. Most of the compounds were found within acceptable range for pharmacokinetic parameters. This work provides the extremely useful leads for structural substituents essential for benzimidazole moiety to exhibit antagonistic activity against corticotropin releasing factor-1 receptors. ? 2017 Informa UK Limited, trading as Taylor & Francis Group.en_US
dc.identifier.citationKumar, N., Mishra, S. S., Sharma, C. S., Singh, H. P., & Kalra, S. (2018). In silico binding mechanism prediction of benzimidazole based corticotropin releasing factor-1 receptor antagonists by quantitative structure activity relationship, molecular docking and pharmacokinetic parameters calculation. Journal of Biomolecular Structure and Dynamics, 36(7), 1691-1712. doi: 10.1080/07391102.2017.1332688en_US
dc.identifier.doi10.1080/07391102.2017.1332688
dc.identifier.issn7391102
dc.identifier.urihttps://kr.cup.edu.in/handle/32116/1365
dc.identifier.urlhttps://www.tandfonline.com/doi/abs/10.1080/07391102.2017.1332688?journalCode=tbsd20
dc.language.isoen_USen_US
dc.publisherTaylor and Francis Ltd.en_US
dc.subjectBenzimidazoleen_US
dc.subjectEmicerfonten_US
dc.subjectPexacerfonten_US
dc.subjectVerucerfonten_US
dc.subjectCrystal structureen_US
dc.subjectinternal validityen_US
dc.subjectMolecular dockingen_US
dc.subjectpharmacokinetic parametersen_US
dc.subjectProtein targetingen_US
dc.subjectStatistical parameen_US
dc.titleIn silico binding mechanism prediction of benzimidazole based corticotropin releasing factor-1 receptor antagonists by quantitative structure activity relationship, molecular docking and pharmacokinetic parameters calculationen_US
dc.title.journalJournal of Biomolecular Structure and Dynamics
dc.typeArticleen_US

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