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

Durgashivaprasad, Ega and Mathew, Geetha and Sebastian, Sarine and Reddy, Manohar SA and Mudgal, Jayesh and Kutty, Gopalan N (2014) Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-infl ammatory drugs. Indian Journal of Pharmacology, 46 (5). pp. 521-526. ISSN 0253 - 7613

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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-infl ammatory 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 infl ammation. For evaluating sub-acute anti-infl ammatory activity, carrageenan-induced infl ammation in rat air pouch was employed. Complete Freund’s adjuvant-induced arthritis in rats was used as a model of chronic infl ammation. To evaluate in vitro anti-infl ammatory 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 infl ux 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 infl ammation. The o-phenol substitution at position 2 of oxadiazole ring in OSD may be responsible for its better in vivo anti-infl ammatory activity. The ability of the compounds to inhibit LPS-induced pro-infl ammatory mediator release suggests an anti-infl ammatory mechanism targeting LPS-TLR4-NF-κB signalling pathway, which needs to be explored in detail. The disparate effi cacy in vitro and in vivo also requires in-depth evaluation of the pharmacokinetics of these novel oxadiazoles.

Item Type: Article
Uncontrolled Keywords: Inflammation; myeloperoxidase; oxadiazole.
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Manipal
Date Deposited: 18 Sep 2014 09:20
Last Modified: 18 Sep 2014 09:20
URI: http://eprints.manipal.edu/id/eprint/140674

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