Spiroindolone analogues bearing benzofuran moiety as a selective cyclooxygenase COX-1 with TNF-α and IL-6 inhibitors.

To design and discover a new compound can used as a COX with TNF-α and IL-6 inhibitors is highly challenge. A series of spiroindolone-bearing benzofuran moieties were resynthesized from the chalcone-based benzo[]furan with substituted isatin, and amino acids. The requisite spiroindolone analogues were tested for their potential inhibitory activities against lipid metabolizing enzymes such as cyclooxygenase COX-1, COX-2, and the release of pro-inflammatory cytokines interleukin IL-6, and tumor necrosis factor TNF-α. Among the tested compounds, , and exhibited COX-1 inhibitor selectively with percent of inhibition 40.81-83.4% and IC values ranging from 20.42 µM to 38.24 µM. In addition, all the synthesized target compounds possessed lipopolysaccharide-induced TNF-α, and IL-6 expression with a varying degree of COX-1 inhibition. Compounds , , , , and markedly inhibited TNF-α, and IL-6 release in WI-38 fibroblast cells. Molecular docking of the most effective and highly selective compounds were investigated and shown important binding mechanisms which could affect pro-inflammatory enzymes and cytokines via the inhibition of COX-1, COX-2, IL-6, and TNF-α.