NOVEL MULTI-FUNCTIONAL DRUGS FOR THE TREATMENT OF INFLAMMATORY DISEASES

Chronic activation of the immune system and the release of the pro-inflammatory cytokines: TNF-α, IL-6 and interleukin 1β (IL-1β), occurs in a variety of disorders including ulcerative colitis, Crohn’s disease, rheumatoid arthritis, diabetes, atherosclerosis and multiple sclerosis. Drugs that inhibit the excessive release of these cytokines may be of therapeutic benefit in these disorders.

We synthesized a new series of indoline derivatives and assessed their potential for reducing TNF-α and IL-6, elevated in a macrophage cell line by lipopolysaccharide (LPS). We compared the anti-inflammatory activity of indolines substituted with CH₂CH₂CH₂NH₂ or CH₂CH₂COOMe groups at positions 3 or 1. We also assessed the effect of substitution of electron donating or withdrawing groups on the benzo ring on this activity, in compounds where the side chain found at position 1 was CH₂CH₂CONH-i-Pr, CH₂CH₂CH₂OH, CH₂CH₂CH₂NH-i-Pr, CH₂CH₂CH₂NH₂ or CH₂CH₂COOMe.