火把花烷二倍半萜结构修饰与免疫抑制活性研究

	火把花烷二倍半萜结构修饰与免疫抑制活性研究; Study on Structural Modification and Immunosuppressive Activity of Colquhounoids
	符然
导师	黎胜红
摘要	Traditional immunosuppressants play an important role in the treatment of organ transplant rejection and autoimmune diseases. However, due to the lack of selectivity of traditional immunosuppressants such as glucocorticoids and azathioprine on the targets which were extensively expressed in many organs and tissues, these drugs exhibit side effects such as high toxicity etc., which limit their wide application in the clinical. Terpenoids natural products featured with their huge amount as well as their diverse structures, make them exhibit a wide range of biological activities and functions as significant source for the development of new drugs. In spite of sesterterpenoids as the least abundance in the terpenoids family, they exhibit diverse pharmacological effects. 14-epi-Colquhounoid D is the main component of Colquhounoids, which possess unique suructure and potential immunosuppressive activity in vitro. In order to achieve high immunosuppressive activity of 14-epi-Colquhounoid D, we conduct the study on structural optimization as well as structure-activity relationship (SAR) analysis on 14-epi-Colquhounoid D and the result are present in this thesis. The dissertation is composed of two chapters. Chapter 1 summarizes the structural modification, immunosuppressive activity and SAR analysis of 14-epi-Colquhounoid D. A total of 41 derivatives of 14-epi-Colquhounoid D were obtained through chemical modification, of which 21 derivatives have improved immunosuppressive activities. By SAR analysis, we found that the structural modification on the 12-carbonyl and furyl of 14-epi-Colquhounoid D is crucial to improve the immunosuppressive activity. In addition, we also completed the first chemical conversion from 14-epi-Colquhounoid D to the degradation product Norcolquhounoids A, which provides the clue for the study of the biosynthetic pathways of natural terpenoid products. Chapter 2 reviews the discovery, structural modification, clinical application and adverse effects of small molecules with immunosuppressive activity. Small molecule immunosuppressants have been in clinical use since the 1980s, and are mainly used to 火把花烷二倍半萜结构修饰与免疫抑制活性研究 IV treat organ transplant rejection. Traditional immunosuppressants include calcineurin inhibitors, m-TOR inhibitors, cell proliferation inhibitors, and glucocorticoid drugs, but due to the wide expression of molecular targets, traditional immunosuppressants have various adverse effects. With the discovery of new active targets, immunosuppressants with better therapeutic effects and less toxicity are successively marketed, including S1P receptor agonists, JAK inhibitors and PKC inhibitors, and their clinical applications cover organ transplant rejection and autoimmune diseases.
	2021-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74542
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	符然. 火把花烷二倍半萜结构修饰与免疫抑制活性研究, Study on Structural Modification and Immunosuppressive Activity of Colquhounoids[D],2021.

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