Chemical synthesis, structural analysis, and decomposition of N-nitroso bile acid conjugates.
N-nitrosoamides of 7 beta-hydroxylated bile acid conjugates, particularly of the ursodeoxycholic acid family have been synthesized. The products and synthetic intermediates were fully characterized by the results of high-resolution 1H NMR, FT-IR, FABMS and ESI-MS studies. The compounds, N-nitrosoglycoursodeoxycholic acid (NOGUDCA), N-nitrosoglycoursocholic acid (NOGUCA) and N-nitrosoglycodeoxycholic acid (NOGDCA) decomposed between pH 6 and 9 in aqueous buffer solutions, indicating a t1/2 of 5-7 h while N-nitrosotauroursodeoxycholic acid (NOTUDCA) indicated a much longer t1/2 of 15-17 h. These results suggest that the compounds are relatively stable and may enter the enterohepatic circulation. Their decomposition is similar to that of other N-nitrosamides, which generate alkylating agents and thereby act as DNA mutagens.
Dayal
B
B
Medical Service, Veterans Administration Medical Center, East Orange, NJ 07019, USA.
Bhojawala
J
J
Rapole
K R
KR
Pramanik
B N
BN
Ertel
N H
NH
Shefer
S
S
Salen
G
G
D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry; D003840:Deoxycholic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D006207:Half-Life; D009682:Magnetic Resonance Spectroscopy; D009603:Nitroso Compounds / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment
D001647:Bile Acids and Salts; D009603:Nitroso Compounds; D003840:Deoxycholic Acid