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

ABSTRACT: To design and discover a new compound can used as a COX with TNF-? and IL-6 inhibitors is highly challenge. A series of spiroindolone-bearing benzofuran moieties were resynthesized from the chalcone-based benzo[b]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-?. Among the tested compounds, 5a, 5c, 5h, 5i, 5l, and 5p exhibited COX-1 inhibitor selectively with percent of inhibition 40.81-83.4% and IC50 values ranging from 20.42?µM to 38.24?µM. In addition, all the synthesized target compounds possessed lipopolysaccharide-induced TNF-?, and IL-6 expression with a varying degree of COX-1 inhibition. Compounds 5d, 5e, 5f, 5g, and 5k markedly inhibited TNF-?, 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-?.

SUBMITTER: Altowyan MS 

PROVIDER: S-EPMC7182988 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature