| Abstract
| - Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of leukocytes to endothelialcells and is implicated in many inflammatory conditions. Since part of the signal transductionpathway that regulates the activation of VCAM-1 expression is redox-sensitive, compoundswith antioxidant properties may have inhibitory effects on VCAM-1 expression. Novel phenoliccompounds have been designed and synthesized starting from probucol (1). Many of thesecompounds demonstrated potent inhibitory effects on cytokine-induced VCAM-1 expressionand displayed potent antioxidant effects in vitro. Some of these derivatives (4o, 4p, 4w, and4x) inhibited lipopolysaccharide (LPS)-induced secretion of pro-inflammatory cytokines suchas tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 from human peripheralblood mononuclear cells (hPBMCs) in a concentration-dependent manner in vitro and showedantiinflammatory effects in an animal model. Compounds 4ad and 4ae are currently in clinicaltrials for the treatment of rheumatoid arthritis (RA) and prevention of chronic organ transplantrejection, respectively.
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