5,8-二甲基乙酰紫草素衍生物QSAR及分子设计

QSAR and molecular design of 5,8-O-dimethyl acylshikonin derivatives with anti-tumor activity

综合运用密度泛函理论、分子力学、统计学及比较分子力场分析等方法研究了抗肿瘤药物5,8-二甲基乙酰紫草素衍生物的二维(2D)、三维(3D)定量构效关系(QSAR).所建最优2D-QSAR方程的交叉验证系数(q2)和拟合相关系数(R2)分别为0.618和0.736.CoMFA模型的q2和非交叉验证系数(r2)分别为0.703和0.982,预测相关系数R2pred为0.746.结果表明,所建立的2D/3D-QSAR模型都具有良好的统计学意义及合理、可信的预报能力,可以预测未知化合物的活性。基于此研究结果,设计了4个具有较高抗肿瘤活性的新化合物.

Two-dimensional（2D）and three-dimensional（3D）quantitative structure-activity relationships（QSAR）of 22 novel compounds of 5,8-O-dimethyl acylshikonin derivatives against the breast cancer cell line（MCF-7）has been carried out by using a combined method of the Density Functional Theory（DFT）,Molecular Mechanics（MM2）and statistics for 2D,as well as the CoMFA methods for 3D.As to the final 2D-QSAR model,the leave-one-out cross-validated value（q^2）was 0.618,the square of correlation coefficient（R^2）was 0.736.And as to CoMFA model,the corresponding q^2 and the non-cross-validated value（r^2）were 0.703 and 0.982,respectively.The final 2D/3D-QSAR models show good statistical quality and satisfactory predictive ability.Base on the results and discussion,we also designed four novel molecules with satisfied prediction activities for the further experimental validation.