INDQ/NO, a Bioreductively Activated Nitric Oxide Prodrug

Abstract

The design, synthesis, and development of INDQ/NO, a novel nitric oxide (NO) prodrug targeted by a bioreductive trigger, are described. INDQ/NO, an indolequinone-diazeniumdiolate is found to be metabolized to produce NO by DT-diaphorase, a bioreductive enzyme that is overexpressed in certain cancers and hypoxic tumors. Cell-based assays revealed that INDQ/NO induces DNA damage and is a potent inhibitor of cancer cell proliferation.