title: Structure-based design, synthesis and preliminary anti-inflammatory activity of bolinaquinone analogues.
abstract: As a part of our drug discovery efforts we developed a series of simplified derivatives of bolinaquinone (BLQ), a hydroxyquinone marine metabolite, showing potent anti-inflammatory activity. Thirteen new hydroxyquinone derivatives closely related to BLQ were synthesized and tested on mouse macrophage-like RAW 264.7 cell line in order to investigate their ability to modulate the production of Prostaglandin E2 (PGE2). This optimization process led to the identification of three strictly correlated compounds with comparable and higher inhibitory potency than BLQ on PGE2 production. To evaluate the affinity of BLQ and its analogues for hsPLA2, surface plasmon resonance (SPR) experiments were performed.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Petronzi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Filosa
authors.forename: Antonella
authors.initials: A
authors.lastname: Peduto
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Monti
authors.forename: Luigi
authors.initials: L
authors.lastname: Margarucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Massa
authors.forename: Simona Francesca
authors.initials: SF
authors.lastname: Ercolino
authors.forename: Valentina
authors.initials: V
authors.lastname: Bizzarro
authors.forename: Luca
authors.initials: L
authors.lastname: Parente
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.forename: Paolo
authors.initials: P
authors.lastname: de Caprariis
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D012717:Sesquiterpenes; C500927:bolinaquinone; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2