2-Prenylated m-dimethoxybenzenes as potent inhibitors of 15-lipo-oxygenase: inhibitory mechanism and SAR studies.

摘要: 15-lipo-oxygenases are one of the iron-containing proteins capable performing peroxidation unsaturated fatty acids in animals and plants. The critical role enzymes formation inflammations, sensitivities, some cancers has been demonstrated mammals. importance led to development mechanistic studies, product analysis, synthesis inhibitors. In this study, a series allyl prenyl dimethoxybenzenes were synthesized their inhibitory potency against soybean 15-Lipo-oxygenase (L1; EC 1,13,11,12) was determined. Among synthetic compounds, 2,6-dimethoxy-1-isopentenyl-4-methylbenzene, 2,6-dimethoxy-1-geranyl-4-methylbenzene, 2,6-dimethoxy-1-farnesyl-4-methylbenzene showed most potent activity with IC50 values 7.6, 5.3, 0.52 μm, respectively. For SAR studies acceptable relationship between enzyme-ligand interactions. Radical scavenging assessment results apart from indicate that electronic properties major factors for lipo-oxygenase inhibition mentioned compounds. Based on theoretical it suggested CH…O intramolecular hydrogen bond ortho-methoxy oxygen methine atoms is stability 2,6-dimethoxyallyl(or prenyl)benzenes radical via planarity fixation phenyl (or prenyl) pi orbitals.