抗肿瘤药物分子设计及其构效关系研究-应用化学专业毕业论文.docxVIP

ABSTRACTCancer ABSTRACT Cancer iS the most forbitable in the word．Camptothecin compounds(CPTs、are very important anticancer drug lead compounds in the processes of drug design and development．Cyclodextrins fCDs)are very useful in the pharmaceutical industry．They possess a hydrophobic central activity suitable for tlle inclusion of various drug molecules forming non．covalent inclusion complexes without impact of drugs activity．Complex stability constant(K)iS a very important target for CDs inclusion complex．In this paper, the structures of CPTs and inclusion complex of 233 compounds with lB-cyclodextrin(13-CD) have been studied by quantitative structure—activity relationship(QSAR、method based on a new set of norm indexes proposed in previous works of our research group．Here，the OSAR model based on the new norm indexes was developed to predict antitumor activities of the CPTs and the logK of 13-CD complex stability constant．Results shown t11at this norm indexes．based．QSAR model could predict these target well．According to the prediction models of CPTs，the correlation coefficient R and standard deviation S values are 0．8278 to 0．9904 and 0．0802 to 0．4038．respectively．The models successfully explained 68．53％．98．09％of the data．According to the prediction models of 233 compounds with B．CD，results shown that this norm indexes—based．QSAR model could predict 109K well witll R(the correlation coe伍cient)and QI OO(Leave．one．out validation)values of 0．9587 and O．8775．respectively．A comparison with other method demonstrated that our method performed better both in accuracy and stability for predicting 3-CD complex stability constant．The predicted results indicates the prediction model based on the norm index．Can not only predict the chemical activity and physiological activity of compounds，but alSO predict the chemical reaction of compounds． Key words：Anticancer drug，Norm index， Structur-activity relationship， ab initio method 万方数据 目 目 录 1前言 1 1．1定量构效关系 ．．1 1．1．1定量构效关系(QSAR)发