The protein tyrosine phosphatase 1B (PTP1B) is considered as negative regulator of insulin receptor signalling and thus a promising target for the development of new antidiabetic drugs [1]. The crude methanol extract of the rhizome of Thonningia sanguinea showed strong inhibition (13.3% residual PTB1B activity) at 30 µg/ml in an in vitro enzyme assay with human recombinant PTP1B compared to the DMSO vehicle control. Bioactivity guided isolation using different chromatographic techniques including RP-MPLC, SEC (Sephadex LH-20) and semipreparative HPLC yielded 10 different compounds (Fig. 1). All isolated compounds consist of a central chalcone-glucoside-unit differing in the connection position of the sugar unit (position 2’ or 4’ of the chalcone-unit) and the further substitution of the glucose moiety with gallic acid and/or hexahydroxydiphenic acid (HHDP). LC-MS- and 1D- and 2D-NMR experiments were used for structure-elucidation while the presence of D-Glucose in the molecules was confirmed by hydrolysis and GC-MS-analysis of the corresponding thiazolidine derivative. Analysis of the PTP1B inhibition of the isolated compounds at 30 µM (positive control: sodium orthovanadate 10 µM, residual PTB1B activity 21.7%) showed the highest activity for the HHDP-substituted compounds 4, 5 and 8 along with Thonningianin A and B (Fig.1). The strongest effect was observed for Thonningianin A with a residual PTB1B activity of 1.9%. This study is the first description of compounds 2, 3, 4, 5, 7 and 8 and revealed a new biological activity of the previously isolated compounds of Thonningia sanguinea, Thonningianin A and B [2].
Acknowledgments:
The autors thank DAAD (Deutscher Akademischer Austauschdienst) and the program “Strategische Partnerschaften” of the TU Dresden for the financial support.
References:
[1] Combs AP. J Med Chem 2010; 53: 2333-44
[2] Ohtani II, Gotoh N, Tanaka J, Higa T, Gyamfi A, Aniya Y, J. Nat. Prod. 2000; 63: 676-679
