Novel 2,5-disubstituted-1,3,4-oxadiazoles as anti-inflammatory drugs
| Autor: | Sarine Sebastian, Jayesh Mudgal, Geetha Mathew, S.A. Manohar Reddy, Gopalan Kutty Nampurath, Ega Durgashivaprasad |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide medicine.drug_class Freund's Adjuvant Anti-Inflammatory Agents Arthritis Inflammation Pharmacology Carrageenan Nitric Oxide Anti-inflammatory Cell Line Nitric oxide chemistry.chemical_compound Pharmacokinetics In vivo medicine Animals Edema Pharmacology (medical) Rats Wistar Oxadiazoles biology medicine.disease Arthritis Experimental Rats Disease Models Animal myeloperoxidase chemistry Myeloperoxidase Immunology biology.protein Inflammation Mediators medicine.symptom oxadiazole Signal Transduction Research Article |
| Zdroj: | Indian Journal of Pharmacology |
| ISSN: | 0253-7613 |
| DOI: | 10.4103/0253-7613.140584 |
| Popis: | 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-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. |
| Databáze: | OpenAIRE |
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