Korean J Physiol Pharmacol.  2009 Dec;13(6):511-516. 10.4196/kjpp.2009.13.6.511.

Cytotoxic Activity and Three-Dimensional Quantitative Structure Activity Relationship of 2-Aryl-1,8-naphthyridin-4-ones

• Kim YJ
• Kim EA
• Chung ML
• Im C

• KMID: 2285389
• DOI: http://doi.org/10.4196/kjpp.2009.13.6.511

Abstract

A series of substituted 2-arylnaphthyridin-4-one analogues, which were previously synthesized in our laboratory, were evaluated for their in vitro cytotoxic activity against human lung cancer A549 and human renal cancer Caki-2 cells using MTT assay. Some compounds (11, 12, and 13) showed stronger cytotoxicity than colchicine against both tumor cell lines, and compound 13 exhibited the most potent activity with IC50 values of 2.3 and 13.4 micrometer, respectively. Three-dimensional quantitative structure activity relationship (3D-QSAR) studies of comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed. Predictive 3D-QSAR models were obtained with q(2) values of 0.869 and 0.872 and r(2)(ncv) values of 0.983 and 0.993 for CoMFA and CoMSIA, respectively. These results demonstrate that CoMFA and CoMSIA models could be reliably used in the design of novel cytotoxic agents.

Keyword

CoMFA; CoMSIA; Cytotoxicity; MTT; QSAR

MeSH Terms

Cell Line, Tumor
Colchicine
Cytotoxins
Humans
Inhibitory Concentration 50
Kidney Neoplasms
Lung Neoplasms
Quantitative Structure-Activity Relationship
Colchicine
Cytotoxins

Figure

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  Fig. 1. Scatter plot of actual activities versus predicted activities against A549 (A) and Caki-2 (B) tumor cell lines (: training set molecules, ▴: test set molecules).

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  Fig. 2. Contour maps of steric and electrostatic fields in lung cancer A549 (A) and renal cancer Caki-2 (B) cells. Compound 13 is shown inside the field. Color-coding is as follows: Green indicates regions where bulky groups increase activity, whereas yellow indicates regions where bulky groups decrease activity. Blue indicates that positive charge favors high activity, whereas red indicates that negative charge favors high activity.

Reference

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