In VitroInhibition ofHelicobacter pyloriGrowth by Redox Cycling Phenylaminojuglones

Abstract

Infection byHelicobacter pyloriincreases 10 times the risk of developing gastric cancer. Juglone, a natural occurring 1,4-naphthoquinone, preventsH. pylorigrowth by interfering with some of its critical metabolic pathways. Here, we report the design, synthesis, andin vitroevaluation of a series of juglone derivatives, namely, 2/3-phenylaminojuglones, as potentialH. pylorigrowth inhibitors. Results show that 5 out of 12 phenylaminojuglones (at 1.5 μg/mL) were 1.5–2.2-fold more active than juglone. Interestingly, most of the phenylaminojuglones (10 out of 12) were 1.1–2.8 fold more active than metronidazole, a knownH. pylorigrowth inhibitor. The most active compound, namely, 2-((3,4,5-trimethoxyphenyl)amino)-5-hydroxynaphthalene-1,4-dione 7, showed significant higher halo of growth inhibitions (HGI = 32.25 mm) to that of juglone and metronidazole (HGI = 14.50 and 11.67 mm). Structural activity relationships of the series suggest that the nature and location of the nitrogen substituents in the juglone scaffold, likely due in part to their redox potential, may influence the antibacterial activity of the series.