Abstract:
The discovery of new therapeutic agents for inflammation has attracted more attention in recent years. Vanilloids are abundantly present in plants belonging to the Zingiberaceae family, contain a vanillyl group (3-methoxy-4-hydroxy-benzyl group), and possess a wide array of biological properties. Vanilloids contain important pharmacophores, vanillyl moiety; α,-unsaturated carbonyl group and alkyl side chain. However, open chain α,-unsaturated carbonyl groups are known as "promiscuous" because these are not selective in binding to receptors that may result in false-positive activities. In addition the presence of free higher alkyl chain make the compounds very flexible, which may result in decreased or/and non-selective activity. Therefore, in this research the new N-vanillylcyclohex-1-ene-1-caboxamide (1), and N-vanillylcyclopent-1-ene-1-carboxamide (2) were synthesised. These compounds retain the essential pharmacophore features of vanilloids. The essential pharmacophore features in 6-Shogaol are vanillyl group, α,-unsaturated carbonyl group and alkyl side chain containing 6 carbons. The novelty in these compounds is that; α,-unsaturated double bond with respect to a keto group was made endocyclic in 5- and 6- membered rings. The compounds were purified by column chromatography and characterised by 1H-NMR, 13C-NMR, FTIR and Mass Spectra. The toxicity and anti-inflammatory activity of compounds were carried out on RAW 264.7 mouse macrophages and BV2 mouse microgilial cell lines. These two cell lines are most widely studied cell lines to test the anti-inflammatory activity of vanilloids. The concentration range of compounds used
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in this study was 5 - 250 μM. The compounds were found to be non-toxic to both RAW 264.7 and BV2 cells and protected the cells from toxic effects of LPS and IFN- at the higher concentrations. In addition, both compounds had shown similar anti-inflammatory activity in both cell lines at higher concentrations (150 - 250 μM). It was observed that there was no significant difference in anti-inflammatory activities of these compounds.
Key words: Vanilloids, RAW264.7 and BV2 cells, Cytotoxicity, Anti- inflammatory activity.
