POTENT IN VITRO ANTICANCER ACTIVITIES OF RING-EXPANDED (“FAT”) NUCLEOSIDES CONTAINING THE IMIDAZO[4,5-E][1,3]DIAZEPINE RING SYSTEM

Abstract

The ring-expanded (“fat”) nucleoside, 4,8-diamino-6-imino-6H-1-β-D-ribo- furanosylimidazo[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.

ACKNOWLEDGMENT

This research was supported by a research grant (#1RO1 CA71079) from the National Cancer Institute of the National Institutes of Health.