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Year : 2014  |  Volume : 46  |  Issue : 5  |  Page : 521--526

Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs

Ega Durgashivaprasad, Geetha Mathew, Sarine Sebastian, S.A. Manohar Reddy, Jayesh Mudgal, Gopalan Kutty Nampurath 
 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India

Correspondence Address:
Gopalan Kutty Nampurath
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal
India

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«SQ»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«SQ»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-κB 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.


How to cite this article:
Durgashivaprasad E, Mathew G, Sebastian S, Reddy SM, Mudgal J, Nampurath GK. Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs .Indian J Pharmacol 2014;46:521-526


How to cite this URL:
Durgashivaprasad E, Mathew G, Sebastian S, Reddy SM, Mudgal J, Nampurath GK. Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs . Indian J Pharmacol [serial online] 2014 [cited 2022 May 28 ];46:521-526
Available from: https://www.ijp-online.com/article.asp?issn=0253-7613;year=2014;volume=46;issue=5;spage=521;epage=526;aulast=Durgashivaprasad;type=0