2,2′-Bipyridyl based copper complexes down regulate expression of pro-inflammatory cytokines and suppress MAPKs in mitogen induced Peripheral blood mononuclear cells

2,2′-Bipyridyl based copper complex I: [CuC 24H 22N 6O 10] at 10 nM and complex Ia: [Cu 2C 32H 43N 8O 3](PF 6) 4 at 7 nM exhibited 50% inhibition of lymphocyte proliferation and less than 20% cytotoxicity in peripheral blood mononuclear cells (PBMCs). Further, pro-inflammatory cytokines such as TNF-α and IL-1β and pro-inflammatory mediator such as Nitric Oxide (NO) besides inducible Nitric Oxide Synthase (iNOS) were inhibited by the copper complexes. They also down regulated the expression of cyclooxegenase-2 (COX-2), yet another mediator of inflammation. Immunoblot analysis revealed the inhibitory effect of these complexes on phosphorylated forms protein kinases (MAPKs) such as ERK1/2, JNK, and p38 in mitogen induced PBMCs. [Display omitted] 2,2-bipyridyl complexes I and Ia down regulated pro-inflammatory cytokines and mediating enzymes through inhibition of MAP kinases suggesting that the complexes may be potent anti-inflammatory compounds.