Analytical Chemistry Department, Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015 UP, India.
J Mol Model. 2012 Jul;18(7):3389-413. doi: 10.1007/s00894-011-1327-6. Epub 2012 Jan 21.
In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient (r(2)) and the cross-validation regression coefficient (rCV(2)) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation (r(2) = 0.99 and rCV(2) = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values.
在本工作中，通过逐步正向多元线性回归方法，采用留一法（leave-one-out approach），建立了用于预测熊果酸类似物对人肺癌（A-549）和中枢神经系统（CNS）（SF-295）癌细胞系活性的定量构效关系（QSAR）模型。QSAR 模型对人肺癌细胞系（A-549）细胞毒性活性的回归系数（r(2)）和交叉验证回归系数（rCV(2)）分别为 0.85 和 0.80。QSAR 研究表明，最低未占分子轨道（LUMO）能量、环数和溶剂可及表面积与抗癌活性密切相关。同样，QSAR 模型对人中枢神经系统（CNS）癌细胞系（SF-295）的细胞毒性活性也表现出高度相关性（r(2) = 0.99 和 rCV(2) = 0.96），表明偶极向量和溶剂可及表面积与活性密切相关。根据（1）H 和（13）C NMR 光谱数据，对预测对这些癌细胞系具有活性的熊果酸类似物进行了半合成和表征，然后在体外对人肺癌（A-549）和中枢神经系统（SF-295）癌细胞系进行了测试。实验结果与预测值吻合良好。
