Novel cationic and neutral glycocholic acid and polyamine conjugates able to inhibit transporters involved in hepatic and intestinal bile acid uptake.

To obtain novel drugs able to inhibit transporters involved in bile acid uptake, three compounds were synthesized by conjugating N-(3-aminopropyl)-1,3-propanediamine (PA) with one (BAPA-3), two (BAPA-6), or three (BAPA-8) moieties of glycocholic acid (GC) through their carboxylic group. The expected net charge in aqueous solutions was 2+ (BAPA-3), 1+ (BAPA-6), and 0 (BAPA-8). They were purified by liquid chromatography and their purity checked by HPLC before being chemically characterized by elemental analysis, NMR, and FAB-MS.

Evidence for dual effects of DNA-reactive bile acid derivatives (Bamets) on hepatitis B virus life cycle in an in vitro replicative system.

A liver targeting strategy to direct antiviral drugs toward hepatitis B virus (HBV) was investigated. As model drugs we used cisplatin-bile acid derivatives (Bamets) to determine the production of virions by HBV-transfected hepatoblastoma cells (HepG2 2.2.

Relationship between tumor cell load and sensitivity to the cytostatic effect of two novel platinum-bile acid complexes, Bamet-D3 and Bamet-UD2.

Based on the organotropic characteristics of bile acids towards the liver and the intestine, two novel compounds of the Bamet family, containing at least one bile acid moiety bound to platinum(II), have been synthesized and their cytostatic effect compared to their ability to become accumulated in tumor cells of hepato-intestinal origin. Bamet-UD2 [cis-diammine-bis-ursodeoxycholic platinum(II)] induced a marked inhibition of cell growth, which was more marked in human hepatoblastoma HepG2 and mouse hepatoma Hepa 1-6 cells than in rat hepatoma McA-RH7777 and human colon adenocarcinoma LS 174T cells. This effect was similar to that observed for cisplatin and stronger than that previously reported for other members of this family, such as Bamet-H2 and Bamet-R2.