Quinone Bioreductive Prodrugs as Delivery Agents

Mohammed      Jaffar; Nathalie      Abou-Zeid; Li      Bai; Ibrahim      Mrema; Ian      Robinson; Richard      Tanner; Ian   J.   Stratford

doi:10.2174/1567201043334560

Abstract

Quinone bioreductive prodrugs were developed to target the hypoxic or the reductase- rich population of solid tumours. The mechanism of their selective activation is based on their ability to convert the quinone sub-structure to their activated semiquinone or hydroquinone species affording the active species. Recent studies on their biochemical activation process have resulted in their development as delivery agents that can effectively release a potent (but not necessarily a cytotoxic) agent under hypoxic / reductive conditions. This technology platform is currently being used to design / identify, and synthesise novel quinone bioreductive delivery agents to target cancer and other diseses where hypoxia and / or reductive enzymes play a major pathophysiological role.

Keywords: quinone, indolequinone, benzoquinone, naphthoquinone, bioreductive agents, hypoxia-selectivity, delivery agents, oxidoreductive enzymes