Potent in vitro anticancer activities of ring-expanded ("fat") nucleosides containing the imidazo[4,5-e][1,3]diazepine ring system.
The ring-expanded ("fat") nucleoside, 4,8-diamino-6-imino-6H-1-beta-D-ribofuranosylimidazo[4,5-e][1,3]diazepine (1) and its 2',3',5'-tri-O-benzoyl derivative (2) exhibited potent broad spectrum anticancer activities in vitro against a wide variety of human tumor cell lines. The tribenzoyl derivative 2 was found to be considerably more active than the parent nucleoside 1. Further studies using human prostate cancer cells PC-3 and DU-145 suggest that the treatment of exponentially growing culture cells with 1 and 2 leads to marked loss of cell viability in a dose-dependent manner.
Gill
J K
JK
Laboratory for Drug Design and Synthesis, Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland, USA.
Wang
L
L
Bretner
M
M
Newman
R
R
Kyprianou
N
N
Hosmane
R S
RS
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D009705:Nucleosides / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy; D011684:Purine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C120720:4,8-diamino-6-imino-6H-1-ribofuranosylimidazo-4,5-e--1,3-diazepine-5'-triphosphate; D000970:Antineoplastic Agents; D001381:Azepines; D009705:Nucleosides; D011684:Purine Nucleosides