title: Strongylophorines, new protein tyrosine phosphatase 1B inhibitors, from the marine sponge Strongylophora strongilata collected at Iriomote Island.
abstract: A new meroditerpene, 26-O-ethylstrongylophorine-14 (1), was isolated from the Okinawan marine sponge Strongylophora strongilata together with six known strongylophorines: 26-O-methylstrongylophorine-16 (2) and strongylophorines-2 (3), -3 (4), -8 (5), -15 (6), and -17 (7). The structure of 1 was assigned on the basis of its spectroscopic data. Compound 1 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 8.7 μM, while known compounds 2-8 gave IC50 values of 8.5, >24.4, 9.0, 21.2, 11.9, and 14.8 μM, respectively. Oleanolic acid, a positive control, inhibited PTP1B activity at 0.7 μM (IC50). The inhibitory activities of strongylophorines possessing the acetal moiety at C-26 (1, 2, and 6) were stronger than those of the lactone derivatives (3 and 5). This is the first study to demonstrate that meroditerpenes inhibit PTP1B activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan; College of Marine Sciences, Gyeongsang National University, Tongyeong, Kyungnam 650-160, Republic of Korea.
authors.forename: Jong-Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Delfly B
authors.initials: DB
authors.lastname: Abdjul
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan. Electronic address: yamazaki@tohoku-pharm.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Ohgi
authors.initials: O
authors.lastname: Takahashi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kirikoshi
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Ukai
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Namikoshi
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D062312:Islands; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Marine sponge; Meroditerpene; PTP1B inhibitor; Strongylophora strongilata; Strongylophorine