Remedial effects of novel 2,3-disubstituted thiazolidin-4-ones in chemical mediated inflammation

• All three synthesized thiazolidin-4-ones possessed anti-inflammatory activity.
• Inhibited LPS-induced ROS and nitrite generation in RAW264.7 murine macrophages.
• Significantly attenuated IL-6 generation in whole blood assay.
• Among the tested compounds, 4C showed maximum in vitro COX-2 enzyme inhibition.
• 4C reversed the elevated TNF-α, IL-6 and PGE2 in rat air pouch inflammation.

Three thiazolidin-4-one derivatives were synthesized, purified and characterized by chromatographic and spectroscopic methods. In the in vitro assays, these compounds inhibited reactive oxygen species (ROS), nitrite and cytokine generation in RAW 264.7 murine macrophages and whole blood. These derivatives attenuated carrageenan-induced acute inflammation in rats. The most effective compound 4C possessed identical anti-inflammatory action at two doses (50 and 100 mg/kg). Further, the effect of compound 4C on locally induced inflammatory mediators was investigated in carrageenan-induced air pouch inflammation in rats. In this model, compound 4C inhibited the cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-6 (systemic and local). Additionally, compound 4C was able to reduce locally elevated prostaglandin-E2 (PGE2). Inhibition of leukocyte infiltration by compound 4C was correlated with reduced locally released myeloperoxidase (MPO). To conclude, compound 4C corrected the inflammatory condition by negative effect on cytokine (TNF-α, IL-6) network and prostaglandin-E2 generation.

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