Understanding and predicting the potency of ROS-based enzyme inhibitors, exemplified by naphthoquinones and ubiquitin specific protease-2.

ABSTRACT: Recent studies have suggested that selective targeting of overexpressed enzymes in cancer cells by small molecules that induce the formation of reactive oxygen species (ROS) could be a viable approach in cancer therapy. One such example is the inactivation of ubiquitin specific protease-2 (USP2)-an emerging drug target to combat prostate cancer-by β-lapachone, which has been identified to involve oxidation of the catalytic cysteine's thiol residue to sulfinic acid. A rational design of β-lapachone analogs with improved activity requires a much better understanding of the variables that determine ROS production by this class of molecules. This crucial aspect was addressed via modulation of its 1,2-naphthoquinone scaffold and establishment of a structure/activity relationship, regardi

SUBMITTER: Gopinath P 

PROVIDER: S-EPMC5355956 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature