康定鼠尾草中抗血小板活性松香烷二萜的研究

	康定鼠尾草中抗血小板活性松香烷二萜的研究; The abietane diterpenoids from Salvia prattii and their antiplatelet aggregation activity
	夏凡
导师	许刚
摘要	This dissertation mainly discussed the abietane diterpenoids from Salvia prattii and their antiplatelet activity, including four chapters. Chapter 1 presente the phytochemistry studies on the abietane diterpenoids of S. prattii. Chapter 2 is the antiplatelet and vasodilative activity of abietane diterpenoids. Chapter 3 is the synthetic study of abietane type platelet aggregation inhibitors. (1) S. prattii, belonging to the Labiatae family, is widely utilized in traditional Tibetan medicines as an alternative of “Danshen” (S. miltiorrhiza). Totally 74 abietane diterpenoids, including 42 new ones (2 new skeletons involving 4 compounds), were isolated from the roots of this plant. The classes of these compounds include tanshenones, seco-abietane, homo-abietane, nor-abietane, and icetexane diterpenoids. Their structures were determined by analyses of comprehensive NMR and MS spectroscopic data and single-crystal X-ray diffractions. It’s noteworthy that salpratlactones A–B (51–52) are the first pair of cis-trans tautomeric abietane derivatives, characterized with an unprecedented 6/5 fused carbocyclic rings linked to a γ-lactone ring by an exocyclic double bond. Significantly, the tautomers also stand for the first naturally occurring agonists of TTCCs. At the concentration of 10 μM, 51, 52 and their mixture all obviously enhanced the peak currents of Cav3.1 TTCC by the same level (around 30％). Further studies revealed that 51 activated Cav3.1 TTCC in a dose-related manner (1 μM to 100 μM), with the EC50 value of 12.48 μM. In addition, salprattins K–L (35–36) are the first examples of 1,10;4,5-bis-seco-abietane diterpenoids feature with a 6/6/6/6/3 ring system. While salpratlactones N–U (53–60) represent the first examples of 4,5;11,12-bis-seco-abietane diterpenoids from the family Salvia. (2) In order to explore the potential cardiovascular activity of diterpenoids from this traditional medicinal plant, the antiplatelet aggregation, vasodilative, and hypolipidemic activity of abietane diterpenoids were tested. The antiplatelet aggregation activity of 100 abietane diterpenoids were evaluated, 14 compounds possessed significant antiplatelet aggregation activity induced by arachidonic acid (AA). The arachidonic acid metabolic pathway is an important link in the process of antiplatelet aggregation, and it’s regarded as an important antithrombosis target for the development of antiplatelet drugs. Significantly, Compounds 17, 18 and 91 showed the most excellent antiplatelet aggregation activity, with IC50 values 1.03, 1.06, and 2.05 μg/ml, respectively, which were approximately 20-fold better than the positive control aspirin (IC50 27.69 μg/ml). Compoured with aspirin, abietane diterpenoids have unique structures, which are potential to become novel antiplatelet lead compounds. (3) In order to elucidate the mechanism of antiplatelet and structure-activity relationship of active molecule, the synthetic studies of 1-keto-aethiopinonewere carried out.
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74194
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	夏凡. 康定鼠尾草中抗血小板活性松香烷二萜的研究, The abietane diterpenoids from Salvia prattii and their antiplatelet aggregation activity[D],2020.

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