新型饱和脂肪酸胆酸缀合物的合成及抗胆结石活性研究

Synthesis and Study on the Activity of Dissolving Cholesterol Crystallization of New Acid Bile Acid Conjugates

胆结石是常见多发病,但临床缺乏有效的治疗药物.饱和脂肪酸与胆酸的缀合物能有效预防胆固醇结晶、溶解体内胆固醇结石.以胆酸或熊去氧胆酸24位羧基为连接位点,以氨基酸为连接子,通过酰胺键将载体与具有溶石活性的饱和脂肪酸偶联,设计合成了一系列新型脂肪酸胆酸缀合物,其结构经元素分析,IR,1H NMR和MS光谱分析确证.通过测定化合物对模型胆汁溶液胆固醇结晶及模型小鼠胆结石的溶解活性,研究了其体内外溶石活性.

Cholesterol gall-stones are a frequent disease which lack of effective treatment pharmaceuticals. Fatty acid bile acid conjugates （FABAC） are new molecules for improving cholesterol solubilization and preventing cholesterol crystallization in bile. A series of novel FABAC molecules were prepared by conjugation of the carboxyl group of cholic acid or ursodeoxycholic acid with saturated fatty acids of variable chain length using two amide bonds and amino acid as linkers, and the structures of them were confirmed by element analysis, IR, ^1H NMR and MS techniques. The fatty acid bile acid conjugates activity of dissolving cholesterol crystallization was tested in model bile, and the activity of preventing of biliary cholesterol crystallization in vivo was tested in inbred mice.