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Published 2008-07-30 Published on SciPeople2009-05-30 16:09:16 JournalJ. Med. Chem.

Computer-aided discovery of anti-inflammatory thiazolidinones with dual cyclooxygenase/lipoxygenase inhibition
Geronikaki A.A., Lagunin A.A., Hadjipavlou-Litina D.I., Elefteriou P.T., Filimonov D.A., Poroikov V.V., Alam I., Saxena A.K. / Alexey Lagunin , Vladimir Poroikov
J. Med. Chem., 2008, 51 (6), 1601-1609.
Abstract New anti-inflammatory agents possessing dual cyclooxygenase/lipoxygenase (COX/LOX) inhibition were discovered by computer-aided prediction of biological activity for 573 virtually designed chemical compounds. Prediction of biological activity was performed by PASS, and prediction results were analyzed with PharmaExpert software. Nine 2-(thiazole-2-ylamino)-5-phenylidene-4-thiazolidinone derivatives differing by the phenyl group substitution were selected for synthesis and experimental testing as potential COX/LOX inhibitors. Eight tested compounds exhibited anti-inflammatory activity in the carrageenin-induced paw edema. It was shown that seven tested compounds (77.8%) were LOX inhibitors, seven compounds were COX inhibitors (77.8%), and six tested compounds (66.7%) were dual COX/LOX inhibitors. Analysis of lipophilicity of the compounds showed a negative correlation with inhibition of edema formation. The binding modes of the most active compounds of this series (2-(thiazole-2-ylamino)-5-(m-chlorophenylidene)-4-thiazolidinone for COX-1 and COX-2, and 2-(thiazole-2-ylamino)-5-(m-nitrophenylidene)-4-thiazolidinone for 15-LOX) were proposed on the basis of docking studies.


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