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International Journal of Pharmacology

Year: 2005  |  Volume: 1  |  Issue: 1  |  Page No.: 79 - 84

Inhibitory Activities of New Series of 4, 5-diaryl Thiadiazoles Derivatives on Lipopolysaccharide-induced Cox-2 Expression

Seyed Nasser Ostad, Mohsen Amini, Zahra Haghipour, Leila Karimi and Latifeh Navidpour


Recent studies have suggested cyclooxygenase-2 (COX-2) expression as a mechanism involved in carcinogenesis. It has also been suggested that changes in COX-2 expression level can be considered as a possible therapeutic target in tumors. Therefore, it was decided to synthesize a new series of 4, 5-diaryl thiadiazoles (compounds 1-5) as COX-2 inhibitors and evaluate their inhibitory activity on COX-2 expression. The COX-2 expression was induced by lipopolysaccharide (LPS) in bovine aortic endothelial (BAE-1) cells and the protein expression was evaluated by immunocytochemistry (ICC). The inhibitory activity of these compounds has been compared with celecoxib and rofecoxib as selective COX-2 inhibitors and indomethacin as a non-selective COX inhibitor. The cytotoxicity of these compounds was measured in different concentrations (10-3 -103 μg mL-1 ) by trypan blue dye exclusion method. The results showed that the cell viability following exposure to 10-2 μg mL-1 of each one of compounds 1-4 was about 90%. Among all tested compounds, compound 4 at 10-2 μg mL-1 showed significant inhibition on COX-2 expression determined by ICC. This effect of compound 4 was comparable to rofecoxib and celecoxib. It is concluded that, the new synthesized compounds and in particular, the compound 4 can be considered for further evaluation as new COX-2 inhibitors.

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