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

The arylsulfonamides were synthesized from aryl sulfonyl chloride and aromatic amines in dichloromethane in the presence of pyridine. The aryne chemistry was used to prepare diarylsulfonamide from arylsulfonamides and O-silylaryl triflate with CsF in acetonitrile at room temperature for 30 min. The synthesized compounds 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 2.6 to 9.7 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, RT-qPCR and Western-blot analysis revealed that treatment with 5n significantly reduced the expression of pro-inflammatory, inflammatory and macrophage marker's expression (IL-1ß, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that 5n 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.

Recovery of residual metals from jarosite waste using chemical and biochemical processes to achieve sustainability: A state-of-the-art review.

Jarosite is a residue that is generated as a by-product during zinc extraction, and it consists of various types of heavy metal (loid)s such as arsenic, cadmium, chromium, iron, lead, mercury and silver. Due to the huge jarosite turn-over rate, and less efficient and expensive residual metal extraction processes, the zinc-producing industries dispose this waste in landfills. However, the leachate generated from such landfills contains a high concentration of heavy metal (loid)s that could contaminate the nearby water resources and cause environmental concern and human health risk. Various thermo-chemical and biological processes have been developed for the recovery of heavy metals from such waste. In this review, we have discussed all those pyrometallurgical, hydrometallurgical, and biological. Those studies were critically reviewed and compared on the basis of their techno-economic differences. The review indicated that these processes have their own benefits and drawbacks such as overall yield, economic and technical constraints, and the need for more than one process to mobilize multiple metal ions from jarosite. Also, in this review, the residual metal extraction processes from jarosite waste have been linked with the relevant UN Sustainable Development Goals (SDGs), which can be useful for a better approach to sustainable development.