کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1372186 981866 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3
چکیده انگلیسی

The three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on a series of falcipain-3 inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. A training set containing 42 molecules served to establish the QSAR models. The optimum CoMFA and CoMSIA models obtained for the training set were statistically significant with cross-validated correlation coefficients rcv2 (q2) of 0.549 and 0.608, and conventional correlation coefficients (r2) of 0.976 and 0.932, respectively. An independent test set of 12 molecules validated the external predictive power of both models with predicted correlation coefficients (rpred2) for CoMFA and CoMSIA as 0.697 and 0.509, respectively. The docking of inhibitors into falcipain-3 active site using GOLD software revealed the vital interactions and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour maps agree well with the structural characteristics of the binding pocket of falcipain-3 active site, which suggests that the information rendered by 3D-QSAR models and the docking interactions can provide guidelines for the development of improved falcipain-3 inhibitors.

3D-QSAR study with CoMFA and CoMSIA methods was carried out on a series of 2-pyrimidinecarbonitrile derivatives that exhibit activity against falcipain-3. The 3D-QSAR models demonstrated good predictive ability and some key structural factors responsible for antimalarial activity. Molecular docking revealed key interactions between falcipain-3 and inhibitors.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 21, Issue 23, 1 December 2011, Pages 7219–7223
نویسندگان
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