Mohammad Reza Saberi - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Farzin Hadizadeh - Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad , Iran
Mohsen Imenshahidi - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Hadi Shakeri - Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad , Iran
Seyedeh Toktam Ziaee - Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad , Iran
Mohammad Ali Ghafuri - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Ramin Sakhtianchi - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Zohreh Badieyan - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Somieh Hajian - School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s) In recent years highly selective COX-۲inhibitors were withdrawn from the market because of an increased risk of cardiovascular complications. In this study we were looking for potent compounds with moderate selectivity for cox-۲. So, four analogues of ۴, ۵-diaryl-۲-(۲-alkylthio-۵-imidazolyl) imidazole derivatives were synthesized and their anti-inflammatory and anti-nociceptive activities were evaluated on male BALB/c mice (۲۵-۳۰ g). Molecular modeling and in vitro COX-۱ and COX-۲ isozyme inhibition studies were also performed. Materials and Methods ۲-(۲-Alkylthio-۵-imidazolyl)-۴,۵-diphenylimidazole compounds were obtained by the reaction of benzyl with ۲-alkylthio-۱-benzylimidazole-۵-carbaldehyde, in the presence of ammonium acetate. Spectroscopic data and elemental analysis of compounds were obtained and their structures elucidated. Anti-nociception effects were examined using writhing test in mice. The effect of the analogues (۷.۵, ۳۰, ۵۲.۵ and ۷۵ mg/kg) against acute inflammation were studied using xylene-induced ear edema test in mice. Celecoxib (۷۵ mg/kg) was used as positive control. Results All four analogues exhibited anti-nociceptive activity against acetic acid induced writhing, but did not show significant analgesic effect (P< ۰.۰۵) compared with celecoxib. It was shown that analogues injected ۳۰ min before xylene application reduced the weight of edematic ears. All analogues were found to have less selectivity for COX-۲ in comparison to celecoxib. Conclusion Injected doses of synthesised analogues possesses favorite anti-nociceptive effect and also has anti inflammatory effects, but comparing with celecoxib this effect is not significantly different. On the other hand selectivity index for analogues is less than celecoxib and so we expect less cardiovascular side effects for these compounds.

Analgesic, Anti-inflammatory, Imidazoles