Discovery of NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors with novel chemical scaffolds by shape-based virtual screening combined with cascade dockingElectronic supplementary information (ESI) available. See DOI: 10.1039/c5ra05919d

A number of novel NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors were discovered from the ChemDiv database via a simple protocol. Based on two reference NQO1 inhibitors, dicoumarol (DIC) and ES936, a shape-based similarity search and cascade docking filtering were conducted to identify new NQO1 inhibitors. Using these techniques, 43 compounds were selected, ordered, and tested. Among them, 7 compounds with novel chemical scaffolds were confirmed to be active by in vitro assays. Determination of the ability for protecting against NQO1-mediated toxicity of β-lapachone (β-lap) confirmed that compounds 8 , 10 and 13 may be pharmacologically useful for probing the function of NQO1 in cells. A number of novel NAD(P)H:quinone oxidoreductase 1 (NQO1) inhibitors were discovered from the ChemDiv database via a simple protocol.