Synthesis and in vitro biological evaluation of N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine (L-alanosine AICO ribonucleoside).
L-Alanosine [3-(hydroxynitrosoamino)-L-alanine] is an antitumor antibiotic that at the present is undergoing phase II clinical trials. Its mode of action as well as its metabolism has been extensively studied, and the metabolite N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosoamino)-L-alanine ribonucleotide (L-alanosine AICOR) proved to be an extremely potent inhibitor of de novo purine biosynthesis and is thus primarily responsible for the antitumor activity of the drug. The synthesis of the corresponding ribonucleoside, i.e., N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine ribonucleoside (L-alanosine AICO ribonucleoside), was accomplished by condensation of a suitably protected derivative of L-alanosine with N-succinimidyl-5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1H-im idazole-4-carboxylate followed by the removal of the protective groups. The biological activity of L-alanosine AICO ribonucleoside was tested in vitro on whole tumor cells and on the isolated enzyme adenylosuccinate synthetase and in vivo on murine experimental leukemia. The compound was found to be inactive in these tests.
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D015470:Leukemia, Myeloid, Acute; D009682:Magnetic Resonance Spectroscopy; D012265:Ribonucleotides / Q000138:chemical synthesis* / Q000633:toxicity; D013055:Spectrophotometry, Infrared
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D012265:Ribonucleotides; C027598:alanosyl-5-amino-4-imidazolecarboxylic acid ribonucleotide