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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
 
ABSTRACT

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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  How to cite this article:

Seyed Nasser Ostad, Mohsen Amini , Zahra Haghipour , Leila Karimi and Latifeh Navidpour , 2005. Inhibitory Activities of New Series of 4, 5-diaryl Thiadiazoles Derivatives on Lipopolysaccharide-induced Cox-2 Expression. International Journal of Pharmacology, 1: 79-84.

DOI: 10.3923/ijp.2005.79.84

URL: https://scialert.net/abstract/?doi=ijp.2005.79.84

REFERENCES
Akarasereenont, P., J.A. Mitchell, Y.S. Bakhle, C. Thiemermann and J.R. Vane, 1995. Comparison of the induction of cyclooxygenase and nitric oxide synthase by endotoxin in endothelial cells and macrophages. Eur. J. Pharmacol., 273: 121-128.
Direct Link  |  

Antoniotti, S., D. Lovisolo, A.F. Pla and L. Munaron, 2002. Expression and functional role of bTRPC1 channels in native endothelial cells. FEBS Lett., 510: 189-195.
PubMed  |  Direct Link  |  

Araki, E., C. Forster, J.M. Dubinsky, M.E. Ross and C. Iadecola, 2001. Cyclooxygenase-2 inhibitor NS-398 protects neuronal cultures from lipopolysaccaride-induced neurotoxicity. Stroke, 32: 2370-2375.
PubMed  |  Direct Link  |  

Bany, B.M. and T.G. Kennedy, 1997. Regulation of cyclooxygenase gene expression in rat endometrial stromal cells: The role of epidermal growth factor. Dev. Genet., 21: 109-115.
PubMed  |  Direct Link  |  

Choi, H.B., C. Khoo, J.K. Ryu, E.V. Breemen, S.U. Kim and J.G. McLarnon, 2002. Inhibition of lipopolysaccaride-induced cyclooxygenase-2, tumor necrosis factor-α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195. J. Neurochem., 83: 546-555.
Direct Link  |  

Cianch, F., C. Cortesini, P. Bechi, O. Fantappie, L. Messerini and A. Vannacci, 2001. Up-regulation of cyclooxygenase-2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology, 121: 1339-1347.
PubMed  |  Direct Link  |  

Fredika, M., M.L. Robertson, F.S. Parrett, M.R. Joarder, M.A.I. Hussein, A. Galal and E.H. Randall, 1998. Ibuprofen-induced inhibition of cyclooxygenase isoform gene expression and regression of rat mammary carcinoma. Cancer Lett., 122: 165-175.
PubMed  |  Direct Link  |  

Gauthier, J.Y., Y. Leblanc, W.C. Black, C. Chan, W.A. Cromlish and R. Gordon, 1996. Synthesis and biological evaluation of 2, 3-diarylthiopen as selective COX-2 inhibitors. PART II: Replacing the heterocycle. Synthesis and biological evaluation of 2, 3-diarylthiopen as selective COX-2 inhibitors. Med. Chem. Lett, 6: 87-92.

Habeeb, A.G., P.N.R. Parveen and E.E. Knaus, 2001. Design and synthesis of 4, 5-diphenyl-4-isoxazolines: Novel inhibitors of cylooxygenase-2 with analgesic and antiinflammatory activity. J. Med. Chem., 44: 2921-2927.

Kurumbail, R.G., A.M. Stevens, J.K. Gierse, J.J. McDonald and R.A. Stegenman et al., 1996. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 384: 644-648.
PubMed  |  Direct Link  |  

Sengupta, S., 1999. Cyclooxygenase-2; A new therapeutic target. Indian J. Pharmacol., 31: 322-332.

Wong, E., C. Deluca, C. Boily, S. Charleson, W. Cromlish and D. Denis, 1997. Characterization of autocrine inducible prostaglandin H synthase-2 (PGHS-2) in human osteosarcoma cells. Inflammat. Res., 46: 51-59.
CrossRef  |  Direct Link  |  

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