Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage. Drug Dev Ind Pharm. 2019 Mar 20;:1-4 Authors: Jin XY, Zhu CB, Fan SY, Sun JL, Shi YC, Wang CH, Wang HF, Zhong BH, Yao YS, Shi WG Abstract Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage. PMID: 30892088 [PubMed - as supplied by publisher]
Source: Drug Development and Industrial Pharmacy - Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research