Authors: SALIMI, Mona¹; GHAHREMANI, Mohammad Hossein²; NADERI, Nima³; AMINI, Mohsen⁴; SALIMI, Elika⁵; AMANLOU, Massoud⁴; ABDI, Khosrou⁴; SALEHI, Raha²; SHAFIEE, Abbas

Source: Acta Pharmacologica Sinica, Volume 28, Number 8, August 2007 , pp. 1254-1260(7)

Publisher: Wiley-Blackwell

Abstract:

Aim: To design and synthesize a series of benzenesulfonamide derivatives, 4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)-yl]benzenesulfonamides(4a-4j), which are intended to act as cyclooxygenase-2 (COX-2) inhibitors with good COX-2 inhibitor activity, and which will exert anti-inflammatory activities in vivo.Methods: Benzenesulfonamide derivatives were designed and synthesized through multi-step chemical reactions. All the synthesized compounds were evaluated in an in vitro assay. The active compound 4a-4f was selected for further evaluation in a carrageenan-induced rat paw edema model. Results: Docking studies showed that compound 4 bind into the primary binding site of COX-2 with the sulfonamide SO₂NH₂ moiety interacting with the secondary pocket amino acid residues. In the in vitro assay, compound 4 inhibited COX-2 with an inhibition concentration IC₅₀ value of 1.23-8 nmol/L, compared to celecoxib with IC₅₀ value of 1.5 nmol/L. Compound 4b and 4c had good potency and selectivity in comparison to the celecoxib. In the in vivo model, compound 4a-4f exhibited a moderate potency to inhibit 50% carrageenan-induced paw edema with value of 1.58-4.3 mg/kg. In the latter experiment, compound 4c was the most active compound. Conclusion: The anti-inflammatory effects obtained for compound 4a-4j could be due to the presence of fluorine or hydrogen substituents in the para position of the phenyl ring of these compounds.

Keywords: cyclooxygenase-2 inhibitor; imidazole; alkylthio; celecoxib

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00619.x

Affiliations: 1: Research and Development Center, Pasteur Institute of Iran, Kasas, Iran 2: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran 3: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran 5: Department of Pharmacology, Faculty of Pharmacy, Mazanderan University of Medical Sciences, Sari, Iran

Publication date: 2007-08-01

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