Synthesis,Antitumor Activity And Molecular Simulation Of Porphyrin-Salicylic Acid Photosensitizer Containing NO Donor

Objective:A series of novel porphyrin-salicylic acid derivatives containing NO donors were synthesized by using salicylic acid and porphyrins as skeletons.A series of biological methods were used to evaluate the preliminary antitumor activity of the obtained compounds.Meanwhile,molecular software was used to understand the mechanism of porphyrin-salicylic acid compounds from the molecular level.Methods:In this study,nitrate ester compound containing NO donor was obtained through nitrification,halogenation and other methods,and then combined with salicylic acid.Porphyrin parent compounds were obtained by one-pot method.A series of porphyrin-salicylic acid derivatives containing NO donors were obtained by combining the parent porphyrin compound with the salicylic acid compound containing NO donor through ester bond.The structures of the target compounds were confirmed by ~1H NMR and MS.MTT assay was used to evaluate the inhibitory effects of the target compounds on human colon cancer HCT-116 cells and human lung cancer A549 cells,respectively,under light and dark conditions.Finally,molecular docking and three-dimensional quantitative conformational studies were used to explore the binding mode and mechanism of the target compound with threonine/serine protein kinase(CDK)and phosphatidylinositol 3-kinase(PI3K).Results:In this study,20 novel porphyrin-salicylic acid derivatives were synthesized and their structures were confirmed by ~1H NMR and MS.The results of MTT assay showed that the novel porphyrin-salicylic acid derivative showed better photodynamic therapeutic effect compared with its porphyrin-parent and salicylic acid monomeric under light,and compounds 9B and 9C showed better inhibitory effect on human colon cancer HCT-116 cells and human lung cancer A549 cells.Molecular simulation results showed that the target compound had a good binding ability to CDK and PI3K protein.Conclusions:In this study,20 novel porphyrin-salicylic acid derivatives containing NO donors were successfully synthesized.Through the molecular simulation study of the obtained compounds and the preliminary study of anti-tumor in vitro,compound 9C showed the significance and value of further study,providing a new direction for the design of new anti-tumor targeted drugs.