Synthesis and evaluation of several oleanolic acid glycoconjugates as protein tyrosine phosphatase 1B inhibitors

• Sixteen oleanolic acid triterpenoid saponins were synthesized.
• The PTP1B and TCPTP inhibitory activity of all compounds were evaluated.
• Compound 1h exhibited remarkable PTP1B inhibitory and good selectivity over TCPTP.

Sixteen novel oleanolic acid triterpenoid saponins were synthesized in an efficient and practical strategy, and their inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) and selectivity over T-cell protein tyrosine phosphatase (TCPTP) were evaluated in vitro. The preliminary structure–activity relationship studies demonstrated that sugar-substituted moiety attached to the C-3 and C-28 positions of OA scaffold greatly affected the inhibitory activity against PTP1B and the selectivity over TCPTP. All the compounds showed inhibitory potencies, and compounds 1h, 1i and 1j exhibited remarkably potent inhibitory activities against PTP1B with IC50 values of 1.03, 0.78 and 3.12 μM, respectively. More significantly, compound 1h showed greater than 4 folds selectivity over highly homologous TCPTP. In parallel, the lipophilicity evaluation of all synthesized compounds was tested as a prediction for pharmacological potency. According to the predicted log P values, the predicted Log P results showed that lipophilicity may correlate with the evaluated biological potency.

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