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为评价四氢黄连碱型季铵化合物降血糖、降血脂的作用,本文以盐酸黄连碱(2)为起始原料,经硼氢化钠还原得到四氢黄连碱,再对其进行季铵化衍生,合成了15个新型黄连碱衍生物4～18,通过1H NMR、HR-MS进行了化学结构确证,并在HepG2细胞葡萄糖消耗模型上评价了所有化合物体外促葡萄糖消耗活性。对于活性较好的化合物进一步评价了其体内降血脂活性。结果表明:化合物5、7、8、9表现出了较好的体外促葡萄糖消耗活性,化合物5、8在高脂血症小鼠和金黄地鼠模型上显示出较好的体内降血脂活性,但作用效果没有阳性对照药辛伐他汀显著。
In order to evaluate the hypoglycemic and hypolipidemic effect of tetrahydropiperazine-based quaternary ammonium compounds, this article takes rhizoma coptishydrochloride (2) as the starting material and is reduced by sodium borohydride to obtain tetrahydropiperazine base, which is then quaternized , 15 new derivatives of Coptidis alkaloids were synthesized. Their chemical structures were confirmed by 1H NMR and HR-MS. The glucose-consuming activity of all compounds in vitro was evaluated on the glucose depletion model of HepG2 cells. The more active compounds were further evaluated for their hypolipidemic activity. The results showed that compounds 5, 7, 8, and 9 showed good in vitro glucose-deprivation activity. Compounds 5 and 8 showed good in vivo hypolipidemic activity in hyperlipidemic mice and golden hamster models, However, the effect of no positive control drug simvastatin significantly.