Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS : Quantitative structure-activity relationships

摘要: Abstract Inhibition of nitric oxide (NO) production by altering the expression induced enzymes involved is potentially an important strategy for obtaining antiinflammatory agents. In search hits to obtain lead compounds new drugs this class, 14 synthetic chalcones derived from 2,4,6-trimethoxyacetophenone were evaluated in terms their inhibitory action, vitro, relation NO murine macrophages line RAW 264.7 bacterial lipopolysaccharides (LPS). All obtained aldolic condensation between acetophenone and corresponding aldehydes, under basic conditions. The mean IC 50 values, calculated through dose versus effect curves, four independent experiments, varied 1.34 27.60 μM, compared with positive control, compound 1400W (IC  = 3.78 μM), a highly selective inhibitor iNOS (induced synthase). Eight gave values less than or equal those 1400W, which suggests that these molecules may act as inhibitors inflammatory process. QSAR study reveals electron-withdrawing groups B-ring seem increase inhibition nitrite production, mainly when position 2. A substitution ortho A-ring seems be necessary activity.