ABSTRACT
Bioassay screening using Indonesian plants, such as traditional foods (vegetables, spices, and tea) and folk medicinal herbs, identified eight protein tyrosine phosphatase (PTP) 1B inhibitory and two antibacterial plants. The leaves of Syzygium polyanthum (Wight) Walp. were examined in more detail to define PTP1B inhibitory components, resulting in the isolation of a new active acylbenzene (1) along with four related congeners of 1 (2-5) and four oleanane triterpenes (6-9). The structure of 1 was elucidated as 12-oxo-12-(2,3,5-trihydroxy-4-methylphenyl)dodecanoic acid based on its spectroscopic data. The acylbenzenes 1 and 3-5 inhibited PTP1B activity with IC50 values ranging between 9.5 and 14 µM, whereas the triterpenes 7-9 also suppressed this activity with IC50 values of 3.3-5.7 µM.
Subject(s)
Phytochemicals , Plant Proteins/metabolism , Plants, Edible/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Syzygium/chemistry , Benzene Derivatives , Gene Expression Regulation, Plant/drug effects , Indonesia , Molecular Structure , Plant LeavesABSTRACT
Two sesquiterpene lactones with the (9R)-eudesman-9,12-olide framework, wedelolides I and J, have been isolated together with five eudesmanolide sesquiterpenes and twelve ent-kaurene diterpenes from the aerial parts of Indonesian Wedelia prostrata. The absolute configurations of wedelolides I and J, proposed in the previous communication, were proven by comparing their experimental Electronic Circular Dichroism (ECD) spectra with the calculated ECD spectrum of wedelolide I. The phytochemical study on the aerial parts of Okinawan Wedelia chinensis led to the isolation of three other eudesmanolide sesquiterpenes in addition to the three sesquiterpenes and eleven diterpenes isolated from the Indonesian W. prostrata as above. However, the wedelolide derivatives found in the Indonesian plant were not detected. Among these compounds, most of the diterpenes inhibited protein tyrosine phosphatase (PTP) 1B activity, and a structure-activity relationship study revealed that the cinnamoyl group enhanced inhibitory activity. Therefore, two ent-kaurene derivatives with and without a cinnamoyl group were examined for the ability to accumulate phosphorylated-Akt (p-Akt) because PTP1B dephosphorylates signal transduction from the insulin receptor such as phosphorylated Akt, a key downstream effector. However, neither compound enhanced insulin-stimulated p-Akt levels in two human hepatoma cell lines (Huh-7 and HepG2) at non-cytotoxic doses.
Subject(s)
Diterpenes/pharmacology , Enzyme Inhibitors/pharmacology , Plant Components, Aerial/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Wedelia/chemistry , Cell Line, Tumor , Diterpenes/chemistry , Diterpenes/isolation & purification , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Hep G2 Cells , Humans , Indonesia , Japan , Molecular Structure , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Structure-Activity RelationshipABSTRACT
Three new sesquiterpenes, 2-deoxy-7-O-methyllemnacarnol (1), 2-deoxy-12 alpha-ethoxy-7-O-methyllemnacarnol (2), and 2-deoxy-12 alpha-methoxy-7-O-methyllemnacarnol (3), were isolated from a soft coral Nephthea sp. collected in Indonesia, together with five known sesquiterpenes. The structures of the new compounds were assigned on the basis of their spectroscopic data.
