Design, synthesis, and biological evaluation of quinoline (quinolinone) derivatives as NADPH oxidase (NOX) inhibitors

Abstract NADPH oxidase (NOX) is the only enzyme in the human body that can directly produce reactive oxygen species. Recent studies have shown that NADPH oxidase is a very potential target for the treatment of Diabetic Nephropathy (DN). Here, a series of quinoline (quinolinone) derivatives were designed and synthesized based on pharmacophore modelling. And the antiproliferative effect against NRK-49F cell-line was evaluated as their potential anti-DN activity. 19d , the most potent compounds with an effective cell proliferation inhibitory activity (IC 50 = 5.25 uM), showed a promising inhibitory activity on NOXs (IC 50 = 1.12 µM). The 3D-QSAR model based on the anti-proliferation activity of NRK-49F exhibited the good predictive ability. In conclusion, 19d may have therapeutic effects on diabetic nephropathy like other NOX inhibitors in clinical trials.