A novel series of quinazoline compounds (2-14) incorporating biologically active heterocyclic moieties were designed and synthesized. The structure of the newly synthesized compounds was recognized on the basis of elemental analyses, IR, (1)H-NMR, (13)C-NMR and mass spectral data. All compounds were evaluated for their ability to induce the cytoprotective enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) using a quantitative bioassay and a docking study was performed in the Kelch domain of Keap1 obtained from the Protein Data Bank (PDB ID: 4IQK) to explore the ability of the synthesized compounds to block the Nrf2-binding site of Keap1. All of the synthesized compounds showed concentration-dependent inducer activity with potencies in the low- or sub-micromolar range. Compound 12 was the most potent inducer in this new series, with a concentration that doubles the specific activity of NQO1 (CD value) of 70 nM. The identification of this compound offers a new chemical scaffold for future development of highly potent inducers.
|Number of pages||6|
|Journal||Journal of Enzyme Inhibition and Medicinal Chemistry|
|Issue number||Suppl. 1|
|Early online date||1 Apr 2016|
|Publication status||Published - 2016|