Background: Protein tyrosine phosphatases 1B are considered to be a desirable validated
target for therapeutic development of type II diabetes and obesity.
Methods: A new series of imidazolyl flavonoids as potential protein tyrosine phosphatase inhibitors
were synthesized and evaluated.
Results: Bioactive results indicated that some synthesized compounds exhibited potent protein
phosphatase 1B (PTP1B) inhibitory activities at the micromolar range. Especially, compound 8b
showed the best inhibitory activity (IC50=1.0 µM) with 15-fold selectivity for PTP1B over the
closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated that 8b
is cell permeable with lower cytotoxicity. Molecular modeling and dynamics studies revealed the
reason for selectivity of PTP1B over TCPTP. Quantum chemical studies were carried out on these
compounds to understand the structural features essential for activity.
Conclusion: Compound 8b should be a potential selective PTP1B inhibitor.
Keywords: Flavonoid, imidazole, protein tyrosine phosphatase, selectivity, cell viability, molecular modeling.
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