Design, synthesis and biological activity evaluation of regioisomeric spiro-(indoline-isoxazolidines) in the inhibition of TNF-α-induced ICAM-1 expression on human endothelial cells?

MedChemComm Pub Date: 2012-10-12 DOI: 10.1039/C2MD20216F

Abstract

Different regioisomeric spiro-(indoline-isoxazolidines) have been synthesized by the microwave mediated cycloaddition reaction between ethyl(5-fluoro-3-indolylidene)-acetate/ethyl(3-indolylidene)-acetate and the substituted α,N-diphenylnitrones. These compounds were screened for their anti-inflammatory activities through inhibition of TNF-α-induced ICAM-1 expression on human endothelial cells. Spiro-(indoline-isoxazolidine) 9p was found to be the most potent compound in inhibiting the ICAM-1 expression. Furthermore, compound 9p significantly inhibited the adhesion of neutrophils to the endothelium in a concentration-dependent manner and also blocked the translocation of NF-κBp65 subunit from the cytoplasm to the nucleus. We believe that compound 9p could be useful in developing better anti-inflammatory molecules for various inflammatory diseases where NF-κB plays a key role.

Graphical abstract: Design, synthesis and biological activity evaluation of regioisomeric spiro-(indoline-isoxazolidines) in the inhibition of TNF-α-induced ICAM-1 expression on human endothelial cells
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