title: Oscarellin, an Anthranilic Acid Derivative from a Philippine Sponge, Oscarella stillans, as an Inhibitor of Inflammatory Cytokines in Macrophages.
abstract: A new anthranilic acid derivative (1) was isolated from a Philippine sponge, Oscarella stillans (Bergquist and Kelly). The structure of compound 1, named oscarellin, was determined as 2-amino-3-(3'-aminopropoxy)benzoic acid from spectroscopic data and confirmed by synthesis. We examined the immunomodulating effect of compound 1 and its mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Our data indicated that the expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were significantly reduced by the pretreatment of 1 (0.1-10 μM) for 2 h. In addition, compound 1 suppressed activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-termimal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. Compound 1 abrogated LPS-induced nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activities, whereas the induction of activating transcription factor-3 (ATF-3) was increased. Taken together, our results suggest that compound 1 attenuates pro-inflammatory cytokines via the suppression of JNK, ERK, AP-1, and NF-κB and the activation of the ATF-3 signaling pathway.
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Korea.
authors.forename: Ii-Seul
authors.initials: IS
authors.lastname: Kwon
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Korea.
authors.forename: Jong Hwan
authors.identifier: 0000-0002-3731-9539
authors.initials: JH
authors.lastname: Kwak
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Korea.
authors.forename: Suhkneung
authors.identifier: 0000-0002-8333-6268
authors.initials: S
authors.lastname: Pyo
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon 16419, Korea.
authors.forename: Hee-Weon
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: AeRyon
authors.initials: A
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, University of Oklahoma , Norman, Oklahoma 73019, United States.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Schmitz
mesh_terms: D000588:Amines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000737:chemistry / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000737:chemistry / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000737:chemistry / Q000378:metabolism*; D010679:Philippines; D011161:Porifera; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000621552:2-amino-3-(3'-aminopropoxy)benzoic acid; D000588:Amines; D001565:Benzoates; D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases