| As the leading disease in society,cancer is also the disease with the highest mortality rate.In recent years,due to changes in the environment and the diversity of human lifestyles,various types of cancer have shown a tendency of increasing morbidity.The fight against cancer is a work that humans need to urgently study.In previous research reports,natural products have become a new way for humans to treat cancer,and many new anticancer inhibitors have also been born.A large number of previous studies have demonstrated that ginsenosides and their derivatives from Panax ginseng,American ginseng,and third-stage stems and leaves have anti-tumor activity.In particular,a series of studies on 25-OCH3-PPD(AD-1)and 25-OH-PPD(AD-2)and their homologues discovered by our group have for the first time revealed new changes in the structure of ginsenoside side chains.The structure-activity relationship has become a hot topic for structural modification of the derivatives of the dammarane derivatives.As a novel anticancer activity inhibitor,ginsenoside has been increasing in recent years.At the same time,salicylic acid,aspirin is a small group structure that has recently been found to have anticancer activity,and it is also an analgesic small molecule.This project hopes to combine the anticancer activity of ginsenosides and the anticancer analgesic activity of salicylic acid and aspirin to study the dual activity of anticancer analgesia.In this dissertation,the acid hydrolysis product of notoginsenoside was used as the raw material to synthesize esterification with salicylic acid.At the same time,the obtained notoginsenoside salicylic acid derivative was further synthesized to obtain notoginsenoside aspirin derivative for evaluation of anticancer activity.In this dissertation,20 target compounds were designed and synthesized.After structural identification,5 cancer cells(human colon cancer cells(HT-29),gastric cancer cells(BGC-823),cervical cancer cells(Hela),human breast Cancer cells(MCF-7),human lung cancer cells(A549),and 1 normal cell(human ovarian epithelial cells(IOSE144))were evaluated for antitumor activity of the cells.The results showed that the compound S19 of gastric cancer cells(BGC-823)showed a strong inhibitory effect against human colon cancer cells(HT-29)(IC50=5.27 μM and 8.12 μM);for cervical cancer cells(Hela),compound S1 Showed a strong inhibitory effect(IC50=3.23 μM);compound S20 showed strong inhibition against human breast cancer cells(MCF-7)(IC50=2.56μM);compound against human lung cancer cells(A549)S25 showed a strong inhibitory effect(IC50=6.12 μM).At the same time,the compounds showed low toxicity(IC50>100 μM)for the cytotoxicity evaluation of human ovarian epithelial cells(IOSE144).Comprehensive anti-cancer activity evaluation,S1,S18,S19,S25 showed a strong comprehensive anti-tumor activity,while low toxicity,also shows the possibility of further research of the compound.A preliminary structure-activity relationship study showed that S1 has C-3,C-12,and C-25 tri-substituted salicylic acid compounds,and its cancer cell inhibitory activity is significantly stronger than that of other disubstituted or mono-substituted compounds.Explains that there is a quantitative dependence of salicylic acid on the anti-cancer trend.In aspirin substitutions,the number-dependent trend was also shown.S19 is aspirin C-3,C-12 double substitution,and its activity is stronger than other aspirin monosubstitution compounds.At the same time,the results of the above anti-tumor activity show that the aspirin substituted groups of each compound have stronger anti-tumor activity than salicylic acid-substituted compounds.Simultaneously with the anti-tumor activity of the positive control,the four compounds of S1,S18,S19,and S25 had 5-10 times more antitumor activity than the respective parent compound.The possibility of becoming an emerging anti-cancer inhibitor lays the foundation for further research on the mechanism of activity. |
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