CoMFA and CoMSIA Studies on 1,3-Bis(benzylidene)-3,4-dihydro-1H-naphthalen-2-one, 2,6-Bis(benzylidene)cyclohexanone, and 3,5-Bis(benzylidene)-4-piperidone Series of Cytotoxic Compounds

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• 作者：Maulik R. Patel ; Jonathan R. Dimmock ; Tanaji T. Talele
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：47
• 期：6
• 页码：2110 - 2123
• 全文大小：468K
• 年卷期：v.47,no.6(November 2007)
• ISSN：1549-960X

文摘

A number of 1,3-bis(benzylidene)-3,4-dihydro-1H-naphthalen-2-ones, 2,6-bis(benzylidene)cyclohexanones,and 3,5-bis(benzylidene)-4-piperidones possess significant potencies toward L1210, Molt 4/C8, and CEMcell lines. The objective of the current 3D QSAR study is to discover some of the structural parameterswhich govern cytotoxic potencies. The CoMFA models with steric and electrostatic fields provided satisfactorystatistical data [(r²_cv = 0.485, r²_ncv = 0.834, r²_pred = 0.591), (r²_cv = 0.532, r²_ncv = 0.850, r²_pred = 0.729), and(r²_cv = 0.561, r²_ncv = 0.864, r²_pred = 0.666)] in regard to the cytotoxic potencies observed toward L1210,Molt 4/C8, and CEM cell lines, respectively. The CoMSIA model with steric, electrostatic, hydrophobic,and H-bond donor fields exhibited r²_cv = 0.513, r²_ncv = 0.833, and r²_pred = 0.562 for cytotoxic activitytoward L1210 cells, while the best CoMSIA models were obtained by a combination of steric, electrostatic,and hydrophobic fields which yielded statistically significant data [(r²_cv = 0.531, r²_ncv = 0.828, r²_pred =0.652) and (r²_cv = 0.560, r²_ncv = 0.841, r²_pred = 0.729)] to explain the cytotoxicity toward Molt 4/C8 andCEM cells, respectively. The information obtained from the CoMFA and CoMSIA 3D contour maps can beused in the design of more potent cytotoxins.