Theoretical Study On Quantitative Structure-activity Relationship Of Anti-tumor Activity Of 14 Matrine Derivatives

Matrine is one of the most important alkaloids in traditional Chinese medicine Sophora flavescens and Japanese bean root,and it plays an important role in the treatment of tumor diseases.However,relying on plant sources for research and development has certain limitations,such as a small number of species and low bioavailability.Therefore,an important method for obtaining new matrine compounds through chemical modification through chemical methods.Quantitative structure-activity relationship theory is an important tool for studying the relationship between substance structure and its biological activity.It plays a powerful role in promoting the design and development of new drug molecules,and provides a direction for the synthesis of drugs with higher biological activity.The study found that the introduction of double bonds and aromatic rings on the 14-position carbon of matrine can significantly improve its anticancer activity,and its pharmacological effect and structure-activity relationship research will provide great help in the development of new matrine derivatives.In this paper,the Gaussian09 software is used to calculate the structural optimization and structure parameters of the three groups of compounds using the B3LYP/6-31G(d)calculation level under the density functional theory.The modeling parameters are obtained.Establish a quantitative structure-activity relationship model between the molecular structure and biological activity of matrine derivatives.It was found that the structural information of the molecule's front-line orbital energy,electronegativity,inner ring charge,dipole moment and active site charge play a leading role in its biological activity.The specific results of the research include:(1)The structural parameters that play a major role in the anti-tumor activity of the 14-pyrrolemethenyl matrine derivatives are the highest occupied orbital energy,frontal orbital energy gap,electronegativity,softness,total charge of nitrogen atoms in the molecule,and average polarization Rate and atomic charge of the active site,the number of neurons in the input layer,hidden layer and output layer of the BP neural network model is 7,10 and 1,respectively,and the sum of the square error ofthe predicted value of the active model and the experimental value is 0.048.The model verification results show that the established model has a high degree of fit and good predictability,and can be used to predict the biological activity of compounds with similar structures;(2)The structural parameters with the greatest influence on the antitumor activity of the 14-indolmethenyl matrine derivatives are the lowest empty orbital energy,electrophilicity,electronegativity,intramolecular F-ring charge,molecular dipole moment,average polarizability And the atomic charge of the active site,the number of neurons in the input layer,hidden layer and output layer of the BP neural network model is 7,7 and 1,respectively,and the sum of the square error of the predicted value of the active model and the experimental value is 0.064.It can provide directions for the synthesis of new matrine drugs;(3)The structural parameters with the greatest influence on the anti-tumor activity of the 14-position aromatic methylenylthiomatrine derivatives are the highest occupied orbital energy,frontal orbital energy gap,electronegativity,charge of A and C rings in the molecule,dipole moment and The bond length of the active site carbon-carbon bond,the number of neurons in the input layer,hidden layer and output layer of the BP neural network model is 7,4,and 1,respectively,and the sum of the squared errors of the predicted value of the active model and the experimental value is verified It is 0.049.It proves that the quantitative structure-activity relationship model we constructed has good predictive ability,which provides convenience for the development of matrine derivatives with higher antitumor activity.