Development and biological evaluation of C₆₀ fulleropyrrolidine-thalidomide dyad as a new anti-inflammation agent

Research studies in the field of C₆₀ fullerene derivatives have significantly increased due to the broad range of biological activities that were found for these compounds. We designed and prepared a new C₆₀ fullerene hybrid bearing thalidomide as a potential double-action anti-inflammatory agent, capable of simultaneous inhibition of LPS-induced NO and TNF-α production. The C₆₀ fulleropyrrolidine-thalidomide dyad, CLT, was an effective agent to suppress the release of NO and TNF-α by the LPS-stimulated macrophages RAW 264.7. Ten micromolars of CLT effectively inhibited LPS-induced NO and TNF-α production by 47.3 ± 4.2% and 70.2 ± 4% with respected to the control, respectively. Furthermore, preliminary biochemical investigation revealed that CLT was a potent agent to suppress both LPS-induced intracellular ROS production and iNOS expression, and CLT also inhibited the phosphorylation of ERK which is an important protein kinase involved in the activation of TNF-α synthesis in LPS-activated macrophages. We believed that the studies herein would hold promise for future development of a new generation of potent anti-inflammatory agents.