多花蒿烯内酯H等三种萜类化合物 衍生物合成与抗肝癌和降血糖活性

	多花蒿烯内酯H等三种萜类化合物衍生物合成与抗肝癌和降血糖活性; Synthesis, anti-hepatoma cytotoxic and hypoglycemic activities of artemyrianolide H, chepraecoxin A and J306 derivatives
	杨晓烔
导师	陈纪军
摘要	Liver cancer and diabetes mellitus are both high-incidence diseases in the world today. The structure modification of sesquiterpene artemyrianolide H with cytotoxic activity on hepatocarcinoma cells, diterpenoid chepraecoxin A and triterpene J306 against α-glucosidase yielded 153 compounds. Some active compounds were obtained and the structure-activity relationships were preliminarily summarized. Liver cancer is a global disease. Primary hepatic carcinoma is the sixth most common cancer, with a relatively high overall morbidity and mortality rate in our country. Sorafenib as the first against liver cancer drug has been in the market since 2007, and then seven drugs have been approved. Although significant therapeutic progress has been achieved, there were still disadvantages including the high price, serious side effects, and drug resistance. Therefore, new drugs were required for the treatment of HCC. The germacrane-type sesquiterpene artemyrianolide H (AH) obtained from Artemisia myriantha showed obvious cytotoxicity against HepG2 and Huh7 cells. In addition, AH could be obtained by oxidation of a large amount of artemyrianolide D. In order to figure out the structure-activity relationships and search new anti-hepatoma cytotoxic candidates, seventy-two derivatives of AH were synthesized by modifying the ester, introducing active fragments and esterification polymer, and assayed for their cytotoxic activities on HepG2、Huh7 and SK-Hep-1 cells. The IC50 values of fifty compounds against the three cell lines were less than 10 μM. Four compounds (1-47, 1-58, 1-64, 1-65) showed cytotoxicity against HepG2 cell with IC50 values ranging from 0.7 to 1.1 μM, 10.9~15.6 fold higher than AH (10.9 ± 1.2 μM). And seven compounds (1-46, 1-47, 1-50, 1-51, 1-55, 1-56, 1-62) showed cytotoxicity against Huh7 cell with IC50 values ranging from 0.5 to 0.7 μM, 10.3~14.4 fold higher than AH (7.2 ± 0.2 μM). Two compounds (1-22 and 1-46) showed 13.2 and 10.8 fold increase against Sk-Hep-1 cell compared with AH (11.9 ± 0.3 μM). Of them, compound 1-47 showed better activity against HepG2, Huh7 and SK-Hep-1 cells, with IC50 values of 0.7 ± 0.1, 0.6 ± 0.1 and 1.3 ± 0.1 μM, 15.5, 12.0 and 9.2 fold higher than AH, respectively. The primary structure-activity relationships were concluded as: the carbonyl group (C-9) and the double bond (C-11-C-13) were necessary groups, the carboxyl group and the long ester chain on C-2 position resulted in the loss of activity, and the esterified polymer compounds showed relatively better activities. Diabetes is a metabolic disease caused by insufficient insulin secretion or ineffective use of insulin, including type I and type II, of which type II diabetes accounts for more than 90%. Inhibitors of α-glucosidase can retard the digestion of carbohydrates, and thus, control the postprandial blood glucose, which is clinically recognized as the first choice for postprandial hypoglycemic drugs. Protein tyrosine phosphatase 1B (PTP1B) is a key negat
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74524
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	杨晓烔. 多花蒿烯内酯H等三种萜类化合物衍生物合成与抗肝癌和降血糖活性, Synthesis, anti-hepatoma cytotoxic and hypoglycemic activities of artemyrianolide H, chepraecoxin A and J306 derivatives[D],2021.

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