Abstract
Bile acids (BAs) are a family of steroids synthesized from cholesterol in the liver. Among bile acids, ursodeoxycholic acid (UDCA) is the drug of choice for treating primary biliary cirrhosis and dissolving cholesterol gallstones. The clinical effectiveness of UDCA includes its choleretic activity, the capability to inhibit hydrophobic bile acid absorption by the intestine under cholestatic conditions, reducing cholangiocyte injury, stimulation of impaired biliary output, and inhibition of hepatocyte apoptosis. Despite its clinical effectiveness, UDCA is poorly soluble in the gastro-duodeno-jejunal contents, and pharmacological doses of UDCA are not readily soluble in the stomach and intestine, resulting in incomplete absorption. Indeed, the solubility of 20 mg/L greatly limits the bioavailability of UDCA. Since the bioavailability of drug products plays a critical role in the design of oral administration dosages, we investigated the enzymatic esterification of UDCA as a strategy of hydrophilization. Therefore, we decided to enzymatically synthesize a glyceric ester of UDCA bile acid to produce a more water-soluble molecule. The esterification reactions between UDCA and glycerol were performed with an immobilized lipase B from Candida antarctica (Novozym 435) in solvent-free and solvent-assisted systems. The characterization of the UDCA-monoglyceride, enzymatically synthesized, has been performed by 1H-NMR, 13C-NMR, COSY, HSQC, HMBC, IR, and MS spectroscopy.
Highlights
Bile acids, called C24 bile acids, belong to the family of biological steroid derivatives and have been isolated and characterized from bile since the 1950s
Ursodeoxycholic acid (3α, 7β-dihydroxy-5β-cholanoic acid), known as ursodiol, is an active ingredient widely used in clinics to dissolve cholesterol gallstones and to treat cholestatic forms of liver disease including primary biliary cirrhosis
ursodeoxycholic acid (UDCA) has been orally administrated for the treatment of chronic liver diseases in patients with cystic fibrosis (CF)-related cholestasis [5], cholestasis correlated with pregnancy [6], sclerosing cholangitis, chronic active hepatitis, and viral hepatitis [7]
Summary
Called C24 bile acids, belong to the family of biological steroid derivatives and have been isolated and characterized from bile since the 1950s These acids are synthesized from cholesterol, secreted in bile, and stored in the gallbladder. Ursodeoxycholic acid (3α, 7β-dihydroxy-5β-cholanoic acid), known as ursodiol, is an active ingredient widely used in clinics to dissolve cholesterol gallstones and to treat cholestatic forms of liver disease including primary biliary cirrhosis. This secondary bile acid derives from the metabolism of cholic acid by the human intestinal microbiota. UDCA is employed as an anti-inflammatory and antioxidant [9,10], and many UDCA derivatives have been synthesized as hybrid functional compounds with anticancer activity [11]
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