3D-QSAR studies of dihydropyrazole and dihydropyrrole derivatives as inhibitors of human mitotic kinesin Eg5 based on molecular docking
| Autor: | Zhihua Lin, Xingyan Luo, Jin Liu, Wenjuan Yang, Yuanqiang Wang, Mao Shu |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Quantitative structure–activity relationship Stereochemistry Pharmaceutical Science Kinesins Mitosis Quantitative Structure-Activity Relationship Plasma protein binding Field analysis Ligands Article Analytical Chemistry lcsh:QD241-441 Eg5 inhibitors LigandFit docking 3D-QSAR lcsh:Organic chemistry Drug Discovery Humans Pyrroles Physical and Theoretical Chemistry Binding site Binding Sites Chemistry Kinase Organic Chemistry Chemistry (miscellaneous) Docking (molecular) Molecular Medicine Kinesin Protein Binding |
| Zdroj: | Molecules Molecules; Volume 17; Issue 2; Pages: 2015-2029 Molecules, Vol 17, Iss 2, Pp 2015-2029 (2012) |
| ISSN: | 1420-3049 |
| Popis: | Human mitotic kinesin Eg5 plays an essential role in mitoses and is an interesting drug target against cancer. To find the correlation between Eg5 and its inhibitors, structure-based 3D-quantitative structure-activity relationship (QSAR) studies were performed on a series of dihydropyrazole and dihydropyrrole derivatives using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. Based on the LigandFit docking results, predictive 3D-QSAR models were established, with cross-validated coefficient values (q²) up to 0.798 for CoMFA and 0.848 for CoMSIA, respectively. Furthermore, the CoMFA and CoMSIA models were mapped back to the binding sites of Eg5, which could provide a better understanding of vital interactions between the inhibitors and the kinase. Ligands binding in hydrophobic part of the inhibitor-binding pocket were found to be crucial for potent ligand binding and kinases selectivity. The analyses may be used to design more potent EG5 inhibitors and predict their activities prior to synthesis. |
| Databáze: | OpenAIRE |
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