喜树碱及其E环修饰衍生物的量子化学研究

Quantum chemiscal study of camptothecin and its E-Ring modificatory derivatives

目的:对喜树碱E环修饰的23个衍生物进行了结构优化和能量计算,比较它们的稳定性和活性,以便为实验设计合成活性更高的此类衍生物指明方向。方法:采用密度泛函理论(DFT),在6-311G(d,p)基组水平上对研究对象进行了计算,为了得到更精确的能量信息,还计算了QCISD(T)/6-311G(d,p)水平上各物质的能量。结果:化合物6稳定性最强,容易形成分子内氢键;化合物19稳定性最差,不易形成分子内氢键,活性最高。结论:计算结果与临床试验结果一致,该方法用于指导该类化合物的设计合成是可行的。

Objective： The structures of twenty-three E-ring modificatory derivatives of camptothecin were optimized and energy calculated.Their stability and activitys were compared to point out the better way to design the derivatives of such kind with more activity.Methods： The objects of study were optimized at 6-311G（d,p） basis set of density functional theory.In order to obtain more accurate energy information,energy calculations were carried out at QCISD（T）/6-311G（d,p） basis set.Results： Compound six has the best stability among them,is apt to form intramolecular hydrogen bond;compound nineteen has the worst stability but the best activity,is difficult to form intramolecular hydrogen bond.Conclusion： The computed result is in accordance with the result of clinic test,indicating the feasibility of this method for guiding the synthetic design of this sort of medicines.