Investigation of a novel reductively-activatable anticancer prodrug of seco-CBI-TMI, an analog of duocarmycin SA
Townes, H. M.; Summerville, K.; Purnell, B. L.; Hooker, M.; Madsen, E. C.; Hudson, S. J.; Lee, M. Investigation of a novel reductively-activatable anticancer prodrug of seco-CBI-TMI, an analog of duocarmycin SA. Med. Chem. Res. 2002, 11, 248-253.
A bioreductively-activated prodrug of seco-CBI-TMI, compound 1, was designed to take advantage of the reductive environment characteristic of hypoxic tumors and selectively deliver a cytotoxin to these sites. The novel quinone-based prodrug I and its nitrophenol analog were prepared, and upon reduction, uv-vis, cv, and NMR studies confirmed the release of the free drug moiety. However, cellular studies of prodrug 1 did not show an increase in cytotoxic potency in cell lines containing the reducing enzyme DT diaphorase, possibly due to a premature activation of prodrug 1 in cell culture media.
Medicinal Chemistry Research