کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1364006 981526 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
3D-QSAR studies on c-Src kinase inhibitors and docking analyses of a potent dual kinase inhibitor of c-Src and c-Abl kinases
چکیده انگلیسی

Three-dimensional quantitative structure–activity relationship (3D-QSAR) analyses were carried out on quinazoline, quinoline, and cyanoquinoline derivatives inhibiting c-Src kinase. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) 3D-QSAR models were developed. The conventional r2 values for CoMFA and CoMSIA are 0.93 and 0.89, respectively. In addition, a homology model of c-Src kinase with the activation loop resembling the active conformation was constructed using the crystal structure of the kinase domain of Lck. The ATP binding pocket of the active form of c-Src is similar to that of the c-Abl kinase in which the activation loop resembles that of an active form. One of the potent c-Src and c-Abl dual kinase inhibitors (77 or SKI-606) was docked inside the active sites of both c-Src and c-Abl. The orientation and hydrogen bonding interactions of 77 are similar in both kinases. The results of 3D-QSAR analyses and structure based studies will be useful for the design of novel c-Src and c-Abl dual kinase inhibitors.

Predictive 3D-QSAR models were developed for a series of quinazoline and quinoline derivatives inhibiting c-Src kinase. A homology model of the active form of c-Src kinase was also constructed. In addition, docking studies of a potent c-Src and c-Abl dual kinase inhibitor (77) were carried out in the active sites of both enzymes to gain insight into the structural requirements for dual activity for this class of molecules.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 13, Issue 15, 1 August 2005, Pages 4704–4712
نویسندگان
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