title: Identification of PTP1B and α-Glucosidase Inhibitory Serrulatanes from Eremophila spp. by Combined use of Dual High-Resolution PTP1B and α-Glucosidase Inhibition Profiling and HPLC-HRMS-SPE-NMR.
abstract: According to the International Diabetes Federation, type 2 diabetes (T2D) has reached epidemic proportions, affecting more than 382 million people worldwide. Inhibition of protein tyrosine phosphatase-1B (PTP1B) and α-glucosidase is a recognized therapeutic approach for management of T2D and its associated complications. The lack of clinical drugs targeting PTP1B and side effects of the existing α-glucosidase drugs, emphasize the need for new drug leads for these T2D targets. In the present work, dual high-resolution PTP1B and α-glucosidase inhibition profiles of Eremophila gibbosa, E. glabra, and E. aff. drummondii "Kalgoorlie" were used for pinpointing α-glucosidase and/or PTP1B inhibitory constituents directly from the crude extracts. A subsequent targeted high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR) analysis and preparative-scale HPLC isolation led to identification of 21 metabolites from the three species, of which 16 were serrulatane-type diterpenoids (12 new) associated with either α-glucosidase and/or PTP1B inhibition. This is the first report of serrulatane-type diterpenoids as potential α-glucosidase and/or PTP1B inhibitors.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Sileshi G
authors.initials: SG
authors.lastname: Wubshet
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Yousof
authors.initials: Y
authors.lastname: Tahtah
authors.affiliation: Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.|Center for Synthetic Biology "bioSYNergy", University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Heskes
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Kenneth T
authors.initials: KT
authors.lastname: Kongstad
authors.affiliation: Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.|Center for Synthetic Biology "bioSYNergy", University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Irini
authors.initials: I
authors.lastname: Pateraki
authors.affiliation: Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.|Center for Synthetic Biology "bioSYNergy", University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Hamberger
authors.affiliation: Plant Biochemistry Laboratory, Department of Plant and Environmental Sciences, University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.|Center for Synthetic Biology "bioSYNergy", University of Copenhagen , Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Birger L
authors.initials: BL
authors.lastname: Møller
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen , Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Staerk
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003924:Diabetes Mellitus, Type 2; D065089:Glycoside Hydrolase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry*; D015394:Molecular Structure; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D028083:Scrophulariaceae; D052616:Solid Phase Extraction; D000520:alpha-Glucosidases / Q000187:drug effects
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D000520:alpha-Glucosidases