Study On The QSAR Of Andrographolide Derivatives

Quantitative structure-activity relationship theory has played a powerful role in promoting the development of drug molecular designing, as a powerful tool to research the relationship between the structure and biological activity, the researchers can evaluate the properties of compounds and screening of the biological activity based on the structure-activity relationship, then synthesize the compounds of highly biological activity purposefully to achieve the effective and reasonable utilization of resources. It also shortens the cycle of research in designing and evaluation of new drugs greatly. So establishing a quantitative structure-activity relationship between molecular structure and properties of drugs has a very important academic significance and practical value.Andrographolide and its derivatives have extensive medicinal physiological functions as one of the main active ingredients of andrographis. Since the limited nature resource, synthesizing the andrographolide drugs by experiment is taken into consideration. In addition to the fewer species of andrographolide pharmaceutic preparation and low bioavailability. Therefore the research of new preparations and synthesizing andrographolide derivatives in chemical methods is an important way to solve the low bioavailability and enhance the clinical efficacy. With the further study of pharmacological action and structure-activity relationship by experimenters, the research and development of andrographolide drugs will be greatly promoted.The paper got two groups of andrographolide derivatives which have anti-cancer and anti-diabetic activity and their activity data through the massive related literature. According to the basis of Density Functional Theory(DFT) at the B3LYP/6-31G(d, p) calculation level by Gaussian software(Gaussian09), the molecular structure and related molecular structure parameters of two groups compounds were optimized and calculated respectively.Then on the basis of the molecular structural parameters of the two groups compounds which had been obtained, the principal component analysis method of the SPSS software were used to screening the main structural parameters. The main structural parameters which include: the orbital energy range,the charge on the ring,the charge of the most activity sites,the length of the most activity sites and dipole moment and so on.Finally, two groups of andrographolide derivatives molecules which have anti-cancer and anti-diabetic activity were verified by neural network model in the MATLAB software respectively. The prediction quadratic sum of error by the method of BP neural network(PRESS values) were 0.042 and 0.063, the results displayed a predictability. A new thought and method for the development of researching and synthesizing better drugs with anti-cancer and anti-diabetic activity are provided.