Synthesis Of Salicylic Acid Kind Of Matrine Derivatives And Their Activities In Anti-Inflammatory And Anti-Tumor

Matrine was a kind of alkaloid, with a broad range of biological activity of its anti-rumor, anti-inflammatory, antiviral, antibacterial, insecticidal, and other pharmacological activities. As the direct anticancer effect of matrine was weak, it was often used clinically in combination with other drugs for middle-late cancers, including lung cancer, liver cancer, stomach cancer, breast cancer and leukemia. Furthermore, arrhythmia, brain injury and liver injury can also be cured by it.Salicylic acid drugs were a kind of chemicals with a wide range of biological activities, such as sterilization, anti-inflammatory, analgesic, antipyretic and so on. It belonged to a class of non-steroidal anti-inflammatory drugs and used clinically for antipyretic, analgesic and anti-inflammatory. In addition, it had certain inhibition for low-risk tumors including pancreatic cancer, lung cancer, ovarian cancer and prostate cancer. The inflammatory bowel disease and hyperglycemia effect can also be treated by it.In this thesis, on the basis of the combination principle of drugs, to develop the activity of matrine, twenty-six novel matrine derivatives were designed and synthesized by the chemical reaction with the introduction of the salicylates. The structure of the target compounds were characterizated and confirmed by1H NMR, IR and MS.The anti-inflammatory activity test results showed that all these derivatives demonstrated that the significant inhibition on xylene-induced ear edema in mice and strong antagonism on carrageenan-induced paw edema in mice. The anti-inflammatory activity of6c,6e,6q showed higher than matrine. The anti-inflammatory activity of these compounds displayed close or lower than matrine. By measuring cell viability of liver cancer cells7402and colorectal cancer cells RKO, the preliminary study of anti-tumor activity of the synthetic matrine derivatives in vitro were investigated. As cisplatin as a positive control, the results showed that all these compounds revealed a superior anti-tumor activity for both cancer cells beyond matrine, but less than cisplatin on RKO;6f,6g,6h,6s these four compounds on cancer survival rates were lower than matrine on two cells, even lower than cisplatin, and its anticancer activity was much higher than matrine, even superior to cisplatin. The anticancer activity of remaining compounds were less than or equivalent matrine.