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|Title:||Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs||Authors:||Mathew, Geetha ;Durgashivaprasad, E.;Sebastian, S.;Reddy, S.A.;Mudgal, J.;Nampurath, G.K.||Issue Date:||2014||Source:||Volume 46, Issue 5, pp. 521 - 526||Journal title:||Indian Journal of Pharmacology||Abstract:||OBJECTIVE: 1,3,4-oxadiazole ring is a versatile moiety with a wide range of pharmacological properties. The present work deals with the synthesis and evaluation of the anti-inflammatory activity of two novel 2,5-disubstituted-1,3,4-oxadiazoles (OSD and OPD). MATERIALS AND METHODS: Carrageenan-induced rat hind paw edema was employed as an acute model of inflammation. For evaluating sub-acute anti-inflammatory activity, carrageenan-induced inflammation in rat air pouch was employed. Complete Freund's adjuvant-induced arthritis in rats was used as a model of chronic inflammation. To evaluate in vitro anti-inflammatory activity, lipopolysaccharide (LPS)-stimulated RAW264.7 cells were used. RESULTS: OSD (100 mg/kg) reduced carrageen-induced paw edema by 60%, and OPD (100 mg/kg) produced a modest 32.5% reduction. OSD also reduced leukocyte influx and myeloperoxidase in carrageenan-induced rat air pouch model. In complete Freund's adjuvant-induced arthritis model, both OSD and OPD (200 mg/kg for 14 days) reduced paw edema and NO levels. In LPS-stimulated RAW264.7 cells, OSD and OPD inhibited formation of nitric oxide and reactive oxygen species, with OPD showing a better activity in comparison to OSD. CONCLUSIONS: OSD was the better of the two compounds in in vivo models of inflammation. The o-phenol substitution at position 2 of oxadiazole ring in OSD may be responsible for its better in vivo anti-inflammatory activity. The ability of the compounds to inhibit LPS-induced pro-inflammatory mediator release suggests an anti-inflammatory mechanism targeting LPS-TLR4-NF-kappaB signalling pathway, which needs to be explored in detail. The disparate efficacy in vitro and in vivo also requires in-depth evaluation of the pharmacokinetics of these novel oxadiazoles.||URI:||https://elibrary.cclhd.health.nsw.gov.au/cclhdjspui/handle/1/1787||DOI:||10.4103/0253-7613.140584||Pubmed:||https://pubmed.ncbi.nlm.nih.gov/25298582/||ISSN:||0253-7613||Publicaton type:||Journal Article||Keywords:||Drug Therapy|
|Appears in Collections:||Health Service Research|
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