Synthesis, activity and molecular modeling of a new series of chromones as low molecular weight protein tyrosine phosphatase inhibitors

Protein Tyrosine phosphatases are crucial elements in eukariotic signal transduction. Several reports suggested that the LMW-PTP family has oncogenic relevance. Moreover, LMW-PTP has been recognized as a negative regulator of insuline-mediated mitotic and metabolic signaling. Thus, inhibition of the LMW-PTP can be considered as an attractive approach for the disogn of new therapeutic agents for the treatment of type II diabetes and for new antitumoral agents. To date, very few (and weak) inhibitors of LMW-TPT have been identified. On the basis of the reported weak activity of some flavonoids on phosphatases, we discovered a lead that originated a new class of active LMW-PTP inhibitors. These compounds inhibit also PTP-1B and are active in cellular assays. Docking experiments and SAR highlighted the possible binding mode of these compounds to the enzyme, putting a background for the future optimization of their inhibitory activity and selectivity towards the clesely related enzyme PTP-1B