Quantitative Structure-activity Relationship Of Camptothecin Derivatives Against Tumor

Quantitative Structure-activity Relationship is an important tool in the modern analysis,mainly to explore the relationship between the structure and properties,especially important in drug development,using quantitative structure-activity relationship can get the relationship between the structure and biological activity of the drug molecules,thus to explore the effects of the drug molecules,and then to guide the synthesis of drug molecules,let the synthesis more targeted,reduce the waste of resources and reduce the drug molecule development cycle.Cancer is one of the five fatal diseases in the world,which has been troubling human beings for a long time.Currently,there are many international cancer treatment methods,including surgery,radiotherapy and chemotherapy in the traditional sense,and biological therapy at the present stage,but there are still some deficiencies in the treatment of cancer.Camptothecin and its derivatives in the treatment of cancer has obvious curative effect,it is in cancer cells for inhibition of cancer cell killing S period of division,combination of camptothecin and topoisomerase I generate camptothecin-DNA topoisomerase I-ternary complexes,promote the stability of the composites can be cracking,hinder the DNA strand closing,cause DNA single fracture,form a "barrier",restrain the progress of the replication forks,meet with the ongoing replication forks can cause irreversible double-stranded DNA rupture,resulting in cell death.In this paper,two groups of camptothecin derivative molecules with anti-tumor activity and corresponding activity data were found by referring to a large number of related literatures.Experimental methods: the first step was to optimize the two groups of molecules with Gaussian 09.B3LYP/ 6-31g(d,p)was used for preliminary optimization on the basis of density functional theory.Then B3LYP/ 6-311g(2d,2p)was used for optimization based on the original optimization.The second step is to import the optimized structural parameters into SPSS,and conduct principal component analysis on the optimized data through the principal component analysis module in SPSS,so as to screen out the structural parameters that can affect the biological activity of camptocine derivatives.The third step is to use the BP neural network in MATLAB to verify the neural network model of two groups of camptothecin derivatives with anti-tumor activity.In BP neural network,the squared sum of the prediction errors of the two groups was 0.055826 and 0.019436,respectively.The results showed that the neural network model in this study had a certain degree of predictability.The study of quantitative structure-activity relationship can accelerate drug research and development,and has a good guiding role in the development of camptothecin derivatives.