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Title: | 苯丙醯黃酮鼠李糖苷類化合物之製備作抑制甲型葡萄糖水解酶之研究 Preparation of acylated rhamnosyl flavonoid analogs as α-glucosidase inhibitors |
Authors: | Po-Hung Hsieh 謝伯鴻 |
Advisor: | 李水盛 |
Keyword: | 甲型葡萄糖水解酶,抑制物,苯丙醯黃酮鼠李糖苷,類化合物,松醇,橙皮苷,肉桂酸,肉桂基溴,查爾酮, α-glucosidase inhibitor,natural flavonol O-acylated rhamnosides,pinitol,hesperidin,seco-hesperidin,cinnamyl bromide,cinnamic acid, |
Publication Year : | 2008 |
Degree: | 碩士 |
Abstract: | 甲型葡萄糖水解酶抑制劑是作用在腸道酵素的一種口服降血糖藥物,藉由干擾碳水化合物之代謝進而降低飯後血糖,達到治療糖尿病之功效。近日發現天然物苯丙醯黃酮鼠李糖苷類化合物對此酵素具良好抑制活性,故本研究對此類化合物進行結構活性關係之探討。選用松醇和橙皮苷作為起始物,以肉桂酸和肉桂基溴 (cinnamyl bromide) 進行酯化和醚化反應製備一系列類似物,再利用催化性氫化反應合成相對應之非共軛系統衍生物。
甲型葡萄糖水解酶試驗顯示松醇類衍生物不具此酵素抑制活性,但可增強胰島素促進葡萄糖吸收之活性,其中以 IIC-4 效果最好 (0.97 uM, S.I. = 13.64)。在鹼性條件下橙皮苷開環形成查爾酮 (chalcone) 類化合物 (IVA-2),此類化合物可些微抑制甲型葡萄糖水解酶,其中在橙皮苷之葡萄糖二號位置和肉桂基溴進行醚化反應可增強產物抑制活性 (IVA-4, IC50 = 136.8 uM)。以 IB-1 在正常老鼠進行葡萄糖耐受性試驗後,發現可顯著降低血糖值,再分別以松醇和肉桂酸給藥進行相同試驗,顯示此效果可能是其水解產物松醇和肉桂酸之功效。而橙皮苷和肉桂基溴之醚化產物其相關活性仍待進一步探討。 α-Glucosidase inhibitors (AGH) are one type of oral antihyperglycemic drugs targeting on the enzymes in the small intestine. They block the metabolism of the carbohydrates and lower postprandial glucose level to achieve therapeutic control of diabetes. According to the recent finding of natural flavonol O-acylated rhamnosides to be potent α-glucosidase inhibitors, the structure and activity relationship of such type compounds were explored in this study. Pinitol and hesperidin were chosen as starting materials. Esterification and etherification were undertaken to prepare a series of phenylpropenoyl- and O-phenylpropenyl- pinitols, and hesperidin derivatives. The corresponding non-conjugated derivatives of these compounds were also prepared via catalytical hydrogenation. Bioassay against α-glucosidase showed that cinnamyl- and dihydrocinnamyl- pinitols have no inhibitory activity. However, they could enhance insulin to stimulate glucose uptake, especially compound IIC-4. Dihydro-1,2-seco-hesperidin (IVA-2) showed weak inhibition activity; nevertheless, etherification with cinnamyl bromide at 2-position of the glucosyl residue could increase activity (IVA-4, IC50 = 136.8 uM). Intravenous glucose tolerance test on normal rats indicated that compound IB-1 could reduce the blood glucose level significantly. This could be attributable to the function of pinitol and cinnamic acid, the hydrolytic products of IB-1. The bioactivity of O-cinnamyl- and O-dihydrocinnamyl- hesperidins remains to be disclosed. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/40219 |
Fulltext Rights: | 有償授權 |
Appears in Collections: | 藥學系 |
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