Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of PTP1B and α-glucosidase.

As part of our continuing research to obtain pharmacologically active compounds from Morus alba L. (Moraceae), four Diels-Alder type adducts (DAs) [morusalbins A-D], one isoprenylated flavonoid [albanin T], together with twenty-one known phenolic compounds were isolated from its root bark. The chemical structures were established using NMR, MS, and ECD spectra. The DAs including morusalbins A-D, albasin B, macrourin G, yunanensin A, mulberrofuran G and K, and albanol B exhibited strong inhibitory activities against both protein tyrosine phosphatase 1B (PTP1B) (IC50, 1.90-9.67 μM) and α-glucosidase (IC50, 2.29-5.91 μM). In the kinetic study, morusalbin D, albasin B, and macrourin G showed noncompetitive PTP1B inhibition, with Ki values of 0.33, 1.00, and 1.09 μM, respectively. In contrast, these DAs together with yunanensin A produced competitive inhibition of α-glucosidase, with Ki values of 0.64, 0.42, 2.42, and 1.19 μM, respectively. Furthermore, molecular docking studies revealed that these active DAs have high affinity and tight binding capacity towards the active site of PTP1B and α-glucosidase.