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目的建立比较分子力场分析法(CoMFA)和比较分子相似性指数分析法(CoMSIA)模型,研究茚并异喹啉酮类化合物对前列腺癌细胞DU-145增殖抑制活性的三维定量构效关系。方法选取63个文献报道的茚并异喹啉酮类化合物,采用CoMFA和CoMSIA方法进行研究。在CoMFA研究中,系统考察了分子取向与网格平移对q2值的影响,并基于得到的最优q2值结果,考察了网格点步长对统计结果的影响;在CoMSIA研究中,系统考察了各种分子场组合、网格点步长和衰减因子对模型统计结果的影响。结果衰减因子为0.35,网格点步长为0.15nm时,仅用疏水场就可以得到最佳模型,所建立CoMFA和CoMSIA模型的交叉验证系数q2值分别为0.630和0.635,都具有较强的预测能力。结论 CoMFA和CoMSIA模型的三维等值线图直观地解释了该类化合物的构效关系,阐明了化合物结构中各位置取代基对前列腺癌细胞DU-145增殖抑制活性的影响,为进一步结构优化以提高抗前列腺癌活性提供了重要的理论依据。
OBJECTIVE: To establish a three-dimensional quantitative structure-activity relationship of inosoisoquinolones on the proliferation inhibitory activity of prostate cancer cell DU-145 by using comparative molecular force field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models. Methods 63 indenoquinolones were selected and reported by CoMFA and CoMSIA methods. In the CoMFA study, the effects of molecular orientation and grid shift on the q2 value were systematically investigated. Based on the optimal q2 value obtained, the effect of the grid point step size on the statistical results was investigated. In the CoMSIA study, the system investigation The effects of various molecular field combinations, lattice point steps and attenuation factors on the statistical results of the model were investigated. The results showed that when the attenuation factor was 0.35 and the lattice step was 0.15nm, the best model was obtained by using only the hydrophobic field. The cross validation coefficients q2 of the CoMFA and CoMSIA models were 0.630 and 0.635, respectively, Ability to predict. Conclusion The three-dimensional contour maps of CoMFA and CoMSIA models intuitively explain the structure-activity relationship of these compounds. The effects of substituent groups at various positions on the proliferation inhibitory activity of prostate cancer cell DU-145 were elucidated. For further structural optimization Improve anti-prostate cancer activity provides an important theoretical basis.