Synthesis and Effects of 4,5-Diaryl-2-(2-alkylthio-5-imidazolyl) Imidazoles as Selective Cyclooxygenase Inhibitors

Objective(s)In recent years highly selective COX-2inhibitors were withdrawn from the market because of an increased risk of cardiovascular complications.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-2. So, four analogues of 4, 5-diaryl-2-(2-alkylthio-5-imidazolyl) imidazole derivatives were synthesized and their anti-inflammatory and anti-nociceptive activities were evaluated on male BALB/c mice (25-30 g). Molecular modeling and in vitro COX-1 and COX-2 isozyme inhibition studies were also performed. Materials and Methods2-(2-Alkylthio-5-imidazolyl)-4,5-diphenylimidazole compounds were obtained by the reaction of benzyl with 2-alkylthio-1-benzylimidazole-5-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 (7.5, 30, 52.5 and 75 mg/kg) against acute inflammation were studied using xylene-induced ear edema test in mice. Celecoxib (75 mg/kg) was used as positive control.ResultsAll four analogues exhibited anti-nociceptive activity against acetic acid induced writhing, but did not show significant analgesic effect (P< 0.05) compared with celecoxib. It was shown that analogues injected 30 min before xylene application reduced the weight of edematic ears. All analogues were found to have less selectivity for COX-2 in comparison to celecoxib. ConclusionInjected 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

Antitumor and antibacterial activity of four fractions from Heracleum persicum Desf. and Cinnamomum zeylanicum Blume

At the present study tumor inhibition and antibacterial activity of the essential oils of Heracleum persicum and Cinnamomum zeylanicum was investigated. Methanol and petroleum ether were extracted from C. zeylanicum by potato disk method. These fractions showed cytotoxic effects in brine shrimp lethality assay (BSL). The authors found both H. persicum (57.16%) and C. zeylanicum (72.90%) had inhibition effects on Agrobacterium tumefaciens which induced crown gall tumor on potato disk. These oils also exhibited antitumor activity where IC50 was applied and the values were 2.24 and 1.20 mg/mL, respectively, for H. persicum and C. zeylanicum. C. zeylanicum also inhibited the growth of all tested Gram- positive and Gram-negative strains. In all, the findings of the present study completely correspond to the results obtained in brine shrimp lethality