Korean J Physiol Pharmacol.  2013 Jun;17(3):237-243. 10.4196/kjpp.2013.17.3.237.

Cytotoxic Activity and Quantitative Structure Activity Relationships of Arylpropyl Sulfonamides

• Hwang YJ
• Park SM
• Yim CB
• Im C

• KMID: 1429304
• DOI: http://doi.org/10.4196/kjpp.2013.17.3.237

Abstract

B13 is a ceramide analogue and apoptosis inducer with potent cytotoxic activity. A series of arylpropyl sulfonamide analogues of B13 were evaluated for their cytotoxicity using MTT assays in prostate cancer PC-3 and leukemia HL-60 cell lines. Some compounds (4, 9, 13, 14, 15, and 20) showed stronger activities than B13 in both tumor cell lines, and compound (15) gave the most potent activity with IC50 values of 29.2 and 20.7 microM, for PC-3and HL-60 cells, respectively. Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed to build highly reliable and predictive CoMSIA models with cross-validated q2 values of 0.816 and 0.702, respectively. Our results suggest that long alkyl chains and a 1R, 2R configuration of the propyl group are important for the cytotoxic activities of arylpropyl sulfonamides. Moreover, the introduction of small hydrophobic groups in the phenyl ring and sulfonamide group could increase biological activity.

Keyword

Arylpropanol; Ceramide; Cytotoxicity; QSAR

MeSH Terms

Apoptosis
Cell Line, Tumor
HL-60 Cells
Humans
Inhibitory Concentration 50
Leukemia
Prostatic Neoplasms
Quantitative Structure-Activity Relationship
Sulfonamides
Sulfonamides

Figure

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  Fig. 1 Ceramide, Mapp, B13, and arylpropyl compounds.

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  Fig. 2 Graph of the correlation between experimental and predicted activities for training and test set compounds. (A) Prostate cancer PC-3 cells. (B) Leukemia HL-60 cells. The IC50 values were transformed into pIC50 (-log IC50) values (■: training set compounds, ▲: test set compounds).

• 

  Fig. 3 3D-contour maps of the CoMSIA models with electrostatic, hydrophobic, and hydrogen bond acceptor fields. (A) Prostate cancer PC-3 cells. (B) Leukemia HL-60 cells. Compound (15) is shown within the fields (blue, favorable electrostatic; red, unfavorable electrostatic; yellow, favorable hydrophobic; white, unfavorable hydrophobic; magenta, favorable hydrogen bond acceptor; cyan, unfavorable hydrogen bond acceptor).

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