Inhibition of Protein Tyrosine Phosphatase 1B by Polyphenol Natural Products: Relevant to Diabetes Management

Many biologically active polyphenols have been recognized for their beneficial effects in managing diabetes and their complications. However, the mechanisms behind their functions are poorly understood. As protein-tyrosine phosphatase 1B (PTP1B) has been identified as a target for anti-diabetic agents, the potential inhibitory effects of a dozen structurally diverse polyphenol natural products have been investigated. Among these polyphenols, potent inhibitory activities have been identified for 6 of them with IC50 in micromolar range, while the other polyphenols showed very weak inhibition. A structure-activity relationship (SAR) study and molecular ducking results suggest that both a rigid planar 3-ring backbone and appropriate substitutions of hydroxyl groups benefit the inhibitory activity. The mechanism of inhibition of PTP1B was further investigated by Michaelis-Menten kinetics and the inhibition mode for PTP1B was determined along with the inhibition constant