Organosilicon-containing thiazole derivatives as potential lipoxygenase inhibitors and anti-inflammatory agents

A number of trimethylsiloxyalkyl and trialkylsilylalkyl thiazole derivatives have been evaluated for their anti-inflammatory activity, lipoxygenase inhibiting properties, and cytotoxicity. The investigated compounds have been found to protect in vivo against carrageenin-induced edema, especially 3-(4-trimethylsiloxypiperidin-1-yl)-N-(thiazol-2- yl)-propionamide (21) and 2-amino-3(gamma-trimethylsilylpropyl) thiazolium iodide ( 22), which exhibited good anti-inflammatory activity: 57.2% CPE inhibition in dose of 0.2 mmol/ kg for compound 21 and 55.0% in dose of 0.01 mmol/ kg for compound 22. All the compounds tested inhibited soybean lipoxygenase activity. 2-(4-Trimethylsilyloxypiperidin-1-yl)-N-[4-(p-methoxyphenyl)-thiazol-2-yl]-acetamide (19) was the most potent displaying inhibition against lipoxygenase (ID50 = 0.01 mmol). It also possessed moderate cytotoxic effect (LC50 = 13 mu g/ mL, 3 x 10(-8) mmol/mL) concerning MG-22A cell lines.