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QSAR on the Inhibition Acticity of Flavopiridol Analogues against Breast Cancer MCF-7  

Soung, Min-Gyu (Department of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University)
Joo, Sung-Mo (Department of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University)
Song, Ah-Reum (Department of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University)
Sung, Nack-Do (Department of Applied Biology & Chemistry, College of Agriculture and Life Sciences, Chungnam National University)
Publication Information
Applied Biological Chemistry / v.50, no.3, 2007 , pp. 147-153 More about this Journal
Abstract
To search for a molecular design of a new breast cancerous inhibitory active compound, 2D-QSAR and HQSAR between the substituents of flavopiridol analogues as substrates and their breast cancerous inhibitory activities against MCF-7 cell were analyzed and discussed quantitatively. It was found that the dispersion with molecule and steric hindrance with substituents will have a tremendous impact on the inhibitory activities from the 2D-QSAR model (1). Also, MR constant is better than that of MS constant as animportant factor. The inhibitory activities from 2D-QSAR model (2) were dependent upon the optimum MR constant (MR = 126 $Cm^3/mol$). Optimized HQSAR model (V) exhibited the best predictability of the inhibitory activities based on the cross-validated $r^2_{cv}$($q^2$= 0.583) and non-cross-validated conventional coefficient ($r^2_{ncv}$= 0.982). From the contribution maps, the inhibitory activity by the imino group on $C_9$ atom was higher than that of the hydroxyl group of $C_8$ atom on the A ring in molecule. Therefore, we can confirm that the dispersion by substituents in molecule is the most important factor in inhibitory activities against MCF-7 cell.
Keywords
Breast cancer MCF-7 cell; Flavopiridol analogues; Induction of cell MCF-7; Optimized 2D-QSAR & HQSAR model;
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