Synthesis and Ligand Based 3D-QSAR of 2,3-Bis-benzylidenesuccinaldehyde Derivatives as New Class Potent FPTase Inhibitor, and Prediction of Active Molecules

Bulletin of the Korean chemical society

Nack Do Sung¹  Jong Han Kim¹  Min Gyu Soung¹  Byoung Mog Kwon¹ 

关键词: 2;    3-Bis-benzylidenesuccinaldehydes;    3D-QSAR;    CoMFA;    CoMSIA;    FPTase inhibition activity;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities (pI50) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The statistical qualities of the optimized CoMFA model II (r2cv .= 0.693 and r2ncv .= 0.974) was higher than those of the CoMSIA model II (r2cv. = 0.484 and r2ncv. = 0.928). The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities (pI50) against FPTase will be able to applied new inhibitor design.

【 授权许可】

Unknown