title: Synthesis and biological evaluation of a class of 5-benzylidene-2-phenyl-thiazolinones as potent 5-lipoxygenase inhibitors.
abstract: A class of 5-lipoxygenase (5-LO) inhibitors characterized by a central 5-benzylidene-2-phenyl-thiazolinone scaffold was synthesized as a new series of molecular modifications and extensions of a previously reported series. Compounds were tested in a cell-based and a cell-free assay and furthermore evaluated for their influence on cell viability. The presented substituted thiazolinone scaffold turned out to be essential for both the 5-LO inhibitory activity and the non-cytotoxic profile. With (Z)-5-(4-methoxybenzylidene)-2-(naphthalen-2-yl)-5H-thiazol-4-one (2k, ST1237), a potent, direct, non-cytotoxic 5-LO inhibitor with IC(50) of 0.08 μM and 0.12 μM (cell-free assay and intact cells), we present a promising lead optimization and development for further investigations as novel anti-inflammatory drug.
authors.affiliation: Institute of Pharmaceutical Chemistry, ZAFES/LiFF/OSF Goethe-University Frankfurt, Max-von-Laue-Str. 9, D-60438 Frankfurt am Main, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Barzen
authors.forename: Carmen B
authors.initials: CB
authors.lastname: Rödl
authors.forename: Andreas
authors.initials: A
authors.lastname: Lill
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Bettina
authors.initials: B
authors.lastname: Hofmann
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; D001094:Arachidonate 5-Lipoxygenase