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 (ID(50) = 0.01 mmol). It also possessed moderate cytotoxic effect (LC(50) = 13 microg/mL, 3 x 10(-8) mmol/mL) concerning MG-22A cell lines.
Geronikaki
Athina
A
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Hadjipavlou-Litina
Dimitra
D
Zablotskaya
Alla
A
Segal
Izolda
I