title: Stictamides A-C, MMP12 inhibitors containing 4-amino-3-hydroxy-5-phenylpentanoic acid subunits.
abstract: An extensive study of the secondary metabolites produced by a new Sticta sp. of lichen has led to the isolation of three new compounds containing the 4-amino-3-hydroxy-5-phenylpentanoic acid residue (Ahppa). The structures of stictamides A-C (1-3) were assigned by 2D NMR spectroscopic and chemical methods. Due to extensive epimerization of the Ahppa residue observed after acid hydrolysis, the configuration of this unit was deduced through conversion of 1 to an appropriate derivative and application of our recently developed statine NMR database. Evaluation of stictamide A against a panel of disease-relevant proteases showed that it inhibited MMP12 at 2.3 μM and significantly reduced invasion in the human glioma cell line U87MG. Docking studies suggest that stictamide A inhibits MMP12 by a non-zinc-binding mechanism.
authors.affiliation: Departmentsof Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, United States.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Liang
authors.forename: Analia
authors.initials: A
authors.lastname: Sorribas
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Sulzmaier
authors.forename: Jorge I
authors.initials: JI
authors.lastname: Jiménez
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Thomas
authors.initials: T
authors.lastname: Sauvage
authors.forename: Wesley Y
authors.initials: WY
authors.lastname: Yoshida
authors.forename: Guangyi
authors.initials: G
authors.lastname: Wang
authors.forename: Joe W
authors.initials: JW
authors.lastname: Ramos
authors.forename: Philip G
authors.initials: PG
authors.lastname: Williams
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D053508:Matrix Metalloproteinase 12 / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation
chemical_list: D000596:Amino Acids; D061965:Matrix Metalloproteinase Inhibitors; D010455:Peptides; D011480:Protease Inhibitors; C049986:4-amino-3-hydroxy-5-phenylpentanoic acid; D053508:Matrix Metalloproteinase 12