دورية أكاديمية

3D-QSAR Studies of Dihydropyrazole and Dihydropyrrole Derivatives as Inhibitors of Human Mitotic Kinesin Eg5 Based on Molecular Docking

التفاصيل البيبلوغرافية
العنوان: 3D-QSAR Studies of Dihydropyrazole and Dihydropyrrole Derivatives as Inhibitors of Human Mitotic Kinesin Eg5 Based on Molecular Docking
المؤلفون: Xingyan Luo, Mao Shu, Yuanqiang Wang, Jin Liu, Wenjuan Yang, Zhihua Lin
المصدر: Molecules; Volume 17; Issue 2; Pages: 2015-2029
بيانات النشر: Molecular Diversity Preservation International
سنة النشر: 2012
المجموعة: MDPI Open Access Publishing
مصطلحات موضوعية: Eg5 inhibitors, LigandFit docking, 3D-QSAR
جغرافية الموضوع: agris
الوصف: 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.
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: English
العلاقة: https://dx.doi.org/10.3390/molecules17022015Test
DOI: 10.3390/molecules17022015
الإتاحة: https://doi.org/10.3390/molecules17022015Test
حقوق: https://creativecommons.org/licenses/by/3.0Test/
رقم الانضمام: edsbas.A6368920
قاعدة البيانات: BASE