title: Development and biological evaluation of C(60) fulleropyrrolidine-thalidomide dyad as a new anti-inflammation agent.
abstract: Research studies in the field of C(60) 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 C(60) fullerene hybrid bearing thalidomide as a potential double-action anti-inflammatory agent, capable of simultaneous inhibition of LPS-induced NO and TNF-alpha production. The C(60) fulleropyrrolidine-thalidomide dyad, CLT, was an effective agent to suppress the release of NO and TNF-alpha by the LPS-stimulated macrophages RAW 264.7. Ten micromolars of CLT effectively inhibited LPS-induced NO and TNF-alpha 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-alpha 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.
authors: Graduate Institute of Biotechnology, National Taipei University of Technology, 1, Sec. 3, Chung-Hsiao E. Road, Taipei 106, Taiwan. Ws75624@ntut.edu.tw
authors: Sheng-Tung
authors: ST
authors: Huang
authors: Chia-Shin
authors: CS
authors: Ho
authors: Chun-Mao
authors: CM
authors: Lin
authors: Hsu-Wei
authors: HW
authors: Fang
authors: Yi-Xiang
authors: YX
authors: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D037741:Fullerenes; D008070:Lipopolysaccharides; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D013792:Thalidomide; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; C069837:fullerene C60