title: Anti-inflammatory effects of a triple-bond resveratrol analog: structure and function relationship.
abstract: Resveratrol is a polyphenol found in grapes and red wine, showing well-characterized anti-inflammatory and antiproliferative activities. In order to exceed resveratrol׳s biological effects and to reveal the structural determinants of the molecule׳s activity, numerous derivatives were synthesized recently. Most of these resveratrol analogs vary from the original molecule in the number, position or identity of the phenolic functional groups. Investigation of the analogs provided important data regarding structure-activity relationship of the molecule. With the exception of cis- and trans-resveratrol and the reduced form dihydroresveratrol, little is known about the molecular effects of the stilbene backbone. In the present study we investigated the anti-inflammatory properties of a new, triple-bond resveratrol analog, 3,4',5-trihydroxy-diphenylacetylene (TDPA) on lipopolysaccharide-stimulated RAW macrophages. We found that the analog had weaker antioxidant activity and stronger inhibitory effect on nuclear factor-kappaB activation, and on cyclooxygenase-2, tumor necrosis factor α and interleukin-6 production. It also prevented lipopolysaccharide-induced depolarization of the mitochondrial membrane. In contrast to resveratrol, TDPA increased the phosphorylation of c-Jun N-terminal and p38 mitogen activated protein kinases. In summary, we identified a novel compound with better anti-inflammatory properties than resveratrol. Our results contributed to a better understanding of the structural determinants of resveratrol׳s biological activities.
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Csenge
authors.initials: C
authors.lastname: Antus
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Radnai
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Dombovari
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Fonai
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Avar
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, Semmelweis University, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Matyus
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary.
authors.forename: Boglarka
authors.initials: B
authors.lastname: Racz
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary; MTA-PTE Nuclear and Mitochondrial Interactions Research Group, Pecs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.affiliation: Department of Biochemistry and Medical Chemistry, Medical Faculty, University of Pecs, Pecs, Hungary. Electronic address: balazs.veres@aok.pte.hu.
authors.forename: Balazs
authors.initials: B
authors.lastname: Veres
mesh_terms: D000114:Acetylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000009:adverse effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D012118:Resorcinols / Q000737:chemistry* / Q000494:pharmacology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C000601540:3,4',5-trihydroxydiphenylacetylene; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012118:Resorcinols; D013267:Stilbenes; D000114:Acetylene; D000077185:Resveratrol
keywords: Inflammation; Lipopolysaccharide; Macrophage; NF-kappaB; Resveratrol (PubChem CID: 445154)