Tit Structure-activity Relationship Study and Design of Novel 1, 8-Naphthimide Derivatives as Potential DNA-targeting Chemotherapeutic Agents for Osteosarcoma

Background: 1, 8-naphthimide is a novel tumor inhibitor targeting nuclear DNA, which makes it applicable to the design and development of anti-osteosarcoma drugs. Objective: The aim of this study is to establish a satisfactory model based on 1, 8-naphthimide derivatives that makes reliable prediction as DNA-targeted chemotherapy agents for osteosarcoma. Methods: All compounds are constructed using ChemDraw software and subsequently optimized using Sybyl software. COMSIA method is used to construct QSAR model with the optimized compound in Sybyl software package. A series of new 1, 8-naphthalimide derivatives are designed and their IC50 values are predicted using the QSAR model. Finally, the newly designed compounds are screened according to IC50 values, and molecular docking experiments are conducted on the top ten compounds of IC50. Results: The COMSIA model shows that q² is 0.529 and the optimum number of components is 6. The model has a high r² value of 0.993 and a low SEE of 0.033, with the F value and the r² predicted to be 495.841 and 0.996 respectively. The statistical results and verification results of the model are satisfactory. In addition, analyzing the contour maps is conducive to finding the structural requirements. Conclusion: The results of this study can provide guidance for medical chemists and other related workers to develop targeted chemotherapy drugs for osteosarcoma.