title: Caulerpenyne and related bis-enol esters are novel-type inhibitors of human 5-lipoxygenase.
abstract: Caulerpenyne (CYN) is a sesquiterpene from green algae with known inhibitory properties against soybean lipoxygenase. Here we introduce a detailed structure-activity study elucidating the inhibitory effects of CYN and a library of six synthetic CYN analogues on isolated human 5-lipoxygenase (5-LO) and cellular 5-LO in polymorphonuclear leukocytes. Essential structural elements are identified and a structurally simplified inhibitor is introduced. The modes of 5-LO inhibition by CYN and the synthetic inhibitors cannot be assigned to any of the known categories of lipoxygenase inhibitors. These compounds clearly interfere directly with 5-LO and represent rather small and flexible molecules, with unique structures among 5-LO inhibitors identified thus far.
authors.affiliation: Friedrich Schiller University Jena, Institute for Inorganic and Analytical Chemistry, Bioorganic Analytics, Lessingstraße 8, 07743 Jena (Germany).
authors.forename: Phillipp
authors.initials: P
authors.lastname: Richter
authors.forename: Gregor
authors.initials: G
authors.lastname: Schubert
authors.forename: Anja Maria
authors.initials: AM
authors.lastname: Schaible
authors.forename: Levent
authors.initials: L
authors.lastname: Cavas
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Georg
authors.initials: G
authors.lastname: Pohnert
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry* / Q000378:metabolism; D004952:Esters; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D011485:Protein Binding; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004952:Esters; D016859:Lipoxygenase Inhibitors; D012717:Sesquiterpenes; C097889:caulerpenyne; D001094:Arachidonate 5-Lipoxygenase
keywords: caulerpenyne; inhibition; lipoxygenase; structure activity; synthetic analogues