title: PTP1B inhibitory secondary metabolites from marine-derived fungal strains Penicillium spp. and Eurotium sp.
abstract: The selective inhibition of PTP1B has been widely recognized as a potential drug target for the treatment of type 2 diabetes and obesity. In the course of screening for PTP1B inhibitory fungal metabolites, the organic extracts of several fungal species isolated from marine environments were found to exhibit significant inhibitory effects, and the bioassay-guided investigation of these extracts resulted in the isolation of fructigenine A (1), cyclopenol (2), echinulin (3), flavoglaucin (4), and viridicatol (5). The structures of these compounds were determined mainly by analysis of NMR and MS data. These compounds inhibited PTP1B activity with 50% inhibitory concentration values of 10.7, 30.0, 29.4, 13.4, and 64.0 micrometer, respectively. Furthermore, the kinetic analysis of PTP1B inhibition by compounds 1 and 5 suggested that compound 1 inhibited PTP1B activity in a noncompetitive manner, whereas compound 5 inhibited PTP1B activity in a competitive manner.
authors.affiliation: Hanbang Body-Fluid Research Center, Wonkwang University, Iksan 570-749, Republic of Korea, Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Jae Hak
authors.initials: JH
authors.lastname: Sohn
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Lee
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Hyuncheol
authors.initials: H
authors.lastname: Oh
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism; D001570:Benzodiazepinones / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism*; D055325:Eurotium / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005841:Gentisates / Q000737:chemistry / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D010407:Penicillium / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012623:Seawater / Q000382:microbiology*; D064210:Secondary Metabolism
chemical_list: D000470:Alkaloids; D001570:Benzodiazepinones; D004791:Enzyme Inhibitors; D005841:Gentisates; D006576:Heterocyclic Compounds, 4 or More Rings; C549274:fructigenine A; C044418:cyclopenol; C001132:echinuline; C005001:flavoglaucin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1