title: Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors from an Indonesian ascidian-derived Penicillium verruculosum.
abstract: Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data (1D and 2D NMR, HRMS, UV, CD, and IR). Compound 2 had a linear sesquiterpene moiety and was considered to be the derivative of the biosynthetic precursor for 1 and 3-5. Compounds 1, 3, and 5 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 8.4, 8.5, and 14.9 μM, respectively. Compound 2 showed 40% inhibition at 23.1 μM, while 4 was not active at 20.7 μM.
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: Wataru
authors.initials: W
authors.lastname: Nakayama
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: Yuta
authors.initials: Y
authors.lastname: Izumikawa
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Toraiwa
authors.affiliation: Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Ukai
authors.affiliation: Research Institute, University of Pembangunan Indonesia, Bahu, Manado 95115, Indonesia.
authors.forename: Henki
authors.initials: H
authors.lastname: Rotinsulu
authors.affiliation: Faculty of Mathematic and Natural Sciences and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Defny S
authors.initials: DS
authors.lastname: Wewengkang
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 Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
authors.forename: Remy E P
authors.initials: RE
authors.lastname: Mangindaan
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; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D007214:Indonesia; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010407:Penicillium / Q000737:chemistry* / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry* / Q000302:isolation & purification; D014561:Urochordata / Q000382:microbiology*
chemical_list: D004791:Enzyme Inhibitors; D012717:Sesquiterpenes; C000606401:verruculide A; C000606402:verruculide B; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1
keywords: Ascidian-derived fungus; Inhibitor; Penicillium verruculosum; Protein tyrosine phosphatase 1B; Verruculide