抗癌药10-OAc取代紫杉醇类似物的构效关系研究

Study on the Quantitative Structure-Activity Relationships of 10-OAc -Paclitaxel Analogues

应用MM 3分子力学方法计算了 2 8个 10位OAc取代紫杉醇类似物的优势构象 ,采用MNDO法计算了化合物的电子结构 ,并用回归分析和神经网络 (BP网络 )方法寻找其量化指数与抗癌活性的关系。结果表明 :1)紫杉醇类似物的油水分配系数logP与活性参数间呈较好的抛物线关系 ,说明药物必须具有适当的脂溶性和水溶性才有利。 2 ) 2′碳原子、R2 基团与 3′碳原子直接键连的N原子、O 18、2 OBz中Bz的负电荷越多 ,对活性越有利。神经网络计算得到R =0 975 ,RMS =0 0 976。

To analyze the QSAR of 28 10 OAc paclitaxel analogues,the MM3 geometry optimization and MNDO quantum chemical indexes had been performed.It can be concluded as follows:(1)The relationship between log P values and activities of 10 OAc paclitaxels is parabola.The compounds must have proper hydrophobicity and hydrophilicity.(2)The more negative charge of 2′carbon,nitrogen in R2,O18 and Bz in 2 OBz the paclitaxel analogues have,the higher activities they will have.