N,N‐Diarylsulfonamide Reduces Proinflammatory Cytokine Interleukin‐6 Levels in Cells through Nuclear Factor‐κB Regulation

Abstract

The synthesized sulfonamides were evaluated for cytotoxicity followed by the cytokine/inflammatory marker’s inhibition capability and its mechanism of action in RAW‐264.7 cells. Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions and inflammation‐associated disorders. Hence, reducing the IL‐6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells at 12.5 µM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL‐6 levels was found to be in the range of 9.7 to 2.6 µM. The promising compounds 5y (IC50 of 2.6 µM) and 5n (IC50 of 4.1 µM) along with other derivatives fulfil drug‐likeness parameters laid down by Lipinski’s rule of five. Further, analysis using RTqPCR and Western‐blot analysis revealed that treatment with 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker’s expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that RL‐442 exhibited anti‐inflammatory properties by modulating the nuclear factor‐κB (NF‐κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.

Luteolin alleviates cadmium-induced metabolism disorder through antioxidant and anti-inflammatory mechanisms in chicken kidney

“…IL-6 and IL-8 are the major cytokines produced by the kidney, but IL-8 is the most studied and is thought to participate in glomerulonephritis and inflammatory kidney disease ( McKenzie et al, 2020 ). COX-2 is an enzyme mediating the progression of inflammation ( Babar et al, 2024 ). Cd exposure mediated renal damage with considerably enhanced inflammatory indices, including IL-1β, TNF-α and IL-6, inducible COX-2 activity in rats ( Ijaz et al, 2023 ).…”