QSAR Study of Novel 1, 8-Naphthimide Derivatives Targeting Nuclear DNA

Abstract

Background:: 1, 8-naphthimide is a novel tumor inhibitor targeting nuclear DNA, which can be used to design and develop anti-osteosarcoma drugs. Objective:: Quantitative structure-activity relationship (QSAR) model was established to predict the physical properties of compounds. Method:: In this study, gene expression programming (GEP) was used to build a nonlinear quantitative structureactivity relationship (QSAR) model with descriptors and to predict the activity of a serials novel DNA-targeted chemotherapeutic agents. These descriptors were calculated in CODESSA software and selected from the descriptor pool based on heuristics. Three descriptors were selected to establish a multiple linear regression model. The best nonlinear QSAR model with a correlation coefficient of 0.89 and 0.82 and mean error of 0.02 and 0.06 for the training and test sets were obtained. Result:: The results showed that the model established by GEP had better stability and predictive ability. The small molecular docking experiment of 32 compounds was carried out in SYBYL software, and it was found that compound 7A had reliable molecular docking ability. Conclusion:: The established model reveals the factors affecting the activity of DNA inhibitors and provides direction and guidance for the further design of highly effective DNA-targeting drugs for osteosarcoma.