CoMFA and CoMSIA 3D-QSAR studies on S

详细信息    查看全文

• 作者：Amol Gupte ; John K. Buolamwini
• 关键词：Equilibrative nucleoside transporter ; hENT1 ; Inhibitor ; 3D-QSAR ; CoMFA ; CoMSIA ; Cross validation ; NBMPR analogs
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 January 2009
• 年：2009
• 卷：19
• 期：2
• 页码：314-318
• 全文大小：328 K

文摘

3D-QSAR (CoMFA and CoMSIA) studies were performed on human equlibrative nucleoside transporter (hENT1) inhibitors displaying K_i values ranging from 10,000 to 0.7 nM. Both CoMFA and CoMSIA analysis gave reliable models with q² values >0.50 and r² values >0.92. The models have been validated for their stability and robustness using group validation and bootstrapping techniques and for their predictive abilities using an external test set of nine compounds. The high predictive r² values of the test set (0.72 for CoMFA model and 0.74 for CoMSIA model) reveals that the models can prove to be a useful tool for activity prediction of newly designed nucleoside transporter inhibitors. The CoMFA and CoMSIA contour maps identify features important for exhibiting good binding affinities at the transporter, and can thus serve as a useful guide for the design of potential equilibrative nucleoside transporter inhibitors.