Investigation of a novel reductively-activatable anticancer prodrug of \u3cem\u3eseco\u3c/em\u3e-CBI-TMI, an analog of duocarmycin SA

Abstract

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