Physicochemical and biopharmaceutical characterization of new sulfonamide derivatives of gallic acid

Gallic acid (GA) is known for its antioxidant activity which is restricted due to its low oral permeability. In this project the carboxylic group of (GA) was substituted with sulfonamide group and hydroxyl groups were methylated which resulted insignificantly (p<0.01) increased permeability of 3,4,5-trimethoxybenzenesulfonamide (TMBS) and 3,4,5-trihydroxybenzenesulfonamide (THBS) over GA, in Parallel Artificial Membrane Permeability Assay studies with simulated gastrointestinal fluids and Human intestinal epithelial cells HIEC-6 cells. Biochemical studies confirmed TMBS was O-demethylated by CYP2D6. THBS and GA had increased antioxidant activity with increased concentration in DPPH assay while TMBS indicated lower activity at all tested concentration. The antioxidant activity of TMBS was greater than GA in HIEC-6 cells which mainly related to its O-demethylation by CYP2D6.