3D-QSAR and docking analysis on a series of multi-cyclin-dependent kinase inhibitors using CoMFA, and CoMSIA

Journal of the Iranian Chemical Research

مقاله 4، دوره 4، شماره 4، اسفند 2011، صفحه 235-249   

نویسندگان

Jahan B. Ghasemi^* ؛ Mahnaz Ayati؛ Somayeh Pirhadi؛ Reihaneh Safavi-Sohi

Chemistry Department, Faculty of Sciences, K. N. Toosi University of Technology, Tehran, Iran

چکیده

A series of 42 Pyrazolo[4,3-h]quinazoline-3-carboxamides as multi-cyclin-dependent kinase
inhibitors regarded as promising antitumor agents to complement the existing therapies, was
subjected to a three-dimensional quantitative activity relationship (3D QSAR). Different QSAR
methods, comparative molecular field analysis (CoMFA), CoMFA region focusing, and
comparative molecular similarity indices analysis (CoMSIA), were compared. All these QSARbased
models had good statistical parameters and yielded q2 values of 0.717, 0.806, and 0.557,
respectively. The CoMFA region focusing model provided the highest q2 and r2 values, which
implied the significance of correlation of steric and electrostatic fields with biological activities.
The quality of CoMSIA was slightly lower than that of CoMFA region focusing in terms of q2
and r2 values. The results of 3D contour maps can be useful for the future development of CDKs
inhibitors. The results of 3D QSAR models are in agreement with docking results, and the
statistical parameters of the models explain that the data are well fitted and have high predictive
ability.

کلیدواژه‌ها

CoMFA؛ CoMFA region focusing؛ CoMSIA؛ CDOCKER؛ multi-cyclin-dependent kinase Inhibitors

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