【摘要】 采用量子化学和分子力学方法寻找一类新型促微管蛋白聚合的大环内酯类抗肿瘤药(Epothilones)的优势构象并进行定量构效关系的研究。通过相关性分析得知,分子的偶极矩和核-核排斥能对分子的活性差异性有显著的影响,可以通过改变C12和C15侧链来改变分子的偶极矩从而提高Epothilones的生物活性。此外,C7上的O原子和C15侧链噻唑基团上的N原子的负电荷增加,对Epothilones的生物活性的增大有利。更多还原

【Abstract】 Epothilones are a class of novel microtubule stabilizing agents.By quantum chemistry and molecular mechanics methods,the quantitative structure-activity relationship(QSAR) research was conducted after the optimized conformations were found.It is important for increasing the bioactivities of epothilones to revise the structure at C12 and C15 sidechain to change their dipole moment and nuclear repulsive potentials.In addition,it is favorable to increase the negative charge of O at C7 and N at thiazole in C15 sidechain for increasing the bioactivities of epothilones.更多还原