BackgroundLong-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents.MethodsThe target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates.Results and discussionThe analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score.ConclusionsThe analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.

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Fifty-four canned tuna fish samples corresponding to 10 widely used different brands were purchased from local markets in Tehran, Iran during 2012-2013 and analysed on heavy metals. Mercury was determined by a direct mercury analyser without any sample preparation. For analysis of other elements samples were digested using a microwave apparatus. Lead and cadmium were determined by graphite furnace atomic absorption spectrometry and arsenic via hydride vapour generation. All samples had arsenic and mercury contamination. Arsenic levels showed a range of 0.25-1.42 mg kg(-1), which might be due to lack of national and international limits for arsenic in canned tuna fish. Lead and cadmium were measured in a small number of samples with a mean of 0.053 ± 0.058 mg kg(-1) and 0.013 ± 0.015 mg kg(-1), respectively. Results obtained for these heavy metals in all samples were lower than the corresponding limits, whereas arsenic and mercury contents might raise some attention.

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