Abstract

A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HRMS spectra. All the newly prepared compounds were screened for their potential protein tyrosine phosphatase inhibitory activities. Bioactive assay manifested that most of the azolyl flavonoids exhibited good protein phosphatase 1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed the best inhibitory activity (IC50 = 1.6 μM) with 9.9-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated 6a has lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity.