No abstract

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.

No abstract

No abstract

Purified NADPH:cytochrome c (P-450) reductase (FPT; NADPH-ferrihemoprotein oxidoreductase, EC (for appropriate references, see refs. 9-11). Evidence exists to suggest that alkylation of DNA is the critical lesion in the cytotoxicity of the mitomycins to both hypoxic and oxygenated cells (12, 13).Studies in mice bearing transplanted solid tumors demonstrated the ability of these antibiotics to reach and kill hypoxic cells and, in combination with x-irradiation, to produce additive or greater than additive cytotoxicity to tumor cells without a corresponding increase in toxicity to normal tissues (10,11