College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Korean J Physiol Pharmacol. 2013 Jun;17(3):237-43. doi: 10.4196/kjpp.2013.17.3.237. Epub 2013 Jun 11.
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 µM, 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 q(2) 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.
B13 是一种神经酰胺类似物和凋亡诱导剂，具有很强的细胞毒性。我们评价了一系列 B13 的芳基丙基磺酰胺类似物对前列腺癌 PC-3 和白血病 HL-60 细胞系的细胞毒性，采用 MTT 法进行检测。在这两种肿瘤细胞系中，一些化合物（4、9、13、14、15 和 20）的活性均强于 B13，化合物 15 的活性最强，对 PC-3 和 HL-60 细胞的 IC50 值分别为 29.2 和 20.7 μM。我们进行了三维定量构效关系（3D-QSAR）分析，构建了高度可靠和可预测的 CoMSIA 模型，交叉验证 q(2) 值分别为 0.816 和 0.702。结果表明，芳基丙基磺酰胺的长烷基链和丙基 1R,2R 构型对其细胞毒性活性很重要。此外，苯环和磺酰胺基上引入小的疏水性基团可以提高生物活性。
