The known seco-cucurbitane triterpene, (24E)-3,4-seco-cucurbita-4,24-diene-3,26,29-trioic acid (1), has been isolated as a potent protein tyrosine phosphatase (PTP) 1B inhibitor together with a new analogue, (24E)-3,4-seco-cucurbita-4,24-diene-3-hydroxy-26,29-dioic acid (2), from the fruiting bodies of Russula lepida. Further evaluation of their biological properties against PTPs revealed that compound 1 inhibited T-cell PTP activity similarly to PTP1B and exhibited moderate selectivity against PTP1B over vaccinia H-1-related phosphatase. Moreover, the in vitro growth inhibitory effects of 1 and 2 against three human cancer cell lines were examined in order to evaluate cell-based efficacy. However, neither 1 nor 2 enhanced insulin-stimulated p-Akt levels at non-cytotoxic concentrations.
Keywords: (24E)-3,4-Seco-cucurbita-4,24-diene-3,26,29-trioic acid; Inhibitor; Protein tyrosine phosphatase 1B; Russula lepida; Seco-cucurbitane triterpene.