title: Furanoterpenes, new types of protein tyrosine phosphatase 1B inhibitors, from two Indonesian marine sponges, Ircinia and Spongia spp.
abstract: Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two furanosesterterpenes and a C21 furanoterpene were obtained as new types of PTP1B inhibitors from two Indonesian marine sponges. (7E, 12E, 20Z, 18S)-Variabilin (1) and (12E, 20Z, 18S)-8-hydroxyvariabilin (2) from Ircinia sp. and furospongin-1 (3) from Spongia sp. inhibited PTP1B activity with IC50values of 1.5, 7.1, and 9.9μM, respectively. The inhibitory activity of compound 1 against T-cell PTP (TCPTP) was approximately 2-fold that against PTP1B, whereas the vaccinia H-1-related phosphatase (VHR) inhibitory effects of 1 were 4-fold weaker than that of its PTP1B inhibitory activity. Compounds 1-3 at 50μM did not show cytotoxicity against two human cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1. Compound 1 did not enhance the phosphorylation level of Akt, a key downstream effector of the cascade, in Huh-7 cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan; Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Delfly B
authors.initials: DB
authors.lastname: Abdjul
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan. Electronic address: yamazaki@tohoku-mpu.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Syu-Ichi
authors.initials: SI
authors.lastname: Kanno
authors.affiliation: Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Defny S
authors.initials: DS
authors.lastname: Wewengkang
authors.affiliation: Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Henki
authors.initials: H
authors.lastname: Rotinsulu
authors.affiliation: Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Deiske A
authors.initials: DA
authors.lastname: Sumilat
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Ukai
authors.affiliation: Faculty of Nursing, University of Pembangunan Indonesia, Bahu, Manado 95115, Indonesia.
authors.forename: Magie M
authors.initials: MM
authors.lastname: Kapojos
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Namikoshi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D018345:Mice, Knockout; D011161:Porifera / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D011506:Proteins / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D011506:Proteins; C100625:variabilin; C093369:furospongin 1; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: C21 furanoterpene; Furanosesterterpene; Inhibitor; Marine sponge; Protein tyrosine phosphatase 1B