Synthesis and biological evaluation of a class of 5-benzylidene-2-phenyl-thiazolinones as potent 5-lipoxygenase inhibitors.

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Barzen S, Rodl CB, Lill A, Steinhilber D, Stark H, Hofmann B

Synthesis and biological evaluation of a class of 5-benzylidene-2-phenyl-thiazolinones as potent 5-lipoxygenase inhibitors.

Bioorg Med Chem. 2012 Jun 1;20(11):3575-83. doi: 10.1016/j.bmc.2012.04.003. Epub 2012 Apr 11.

PubMed ID

22551629 [ View in PubMed

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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 muM and 0.12 muM (cell-free assay and intact cells), we present a promising lead optimization and development for further investigations as novel anti-inflammatory drug.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Zileuton	Arachidonate 5-lipoxygenase	IC 50 (nM)	500	N/A	N/A	Details