Unusual eta(2)-Allene Osmacycle with Apoptotic Properties

作者：He, Xumin; Gong, Lei; Kraeling, Katja; Gruendler, Katharina; Frias, Corazon; Webster, Richard D.; Meggers, Eric^*; Prokop, Aram; Xia, Haiping

来源：ChemBioChem, 2010, 11(11): 1607-1613.

DOI：10.1002/cbic.201000055

• antitumor agents
• apoptosis
• cytotoxicity
• metallacycles
• osmium

Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in He La cells led to the discovery of a highly cytotoxic eta(2)-allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a sigma-bond to a carbon in combination with coordination to an allene moiety. The osmacycle strongly induces apoptosis in Burkitt-like lymphoma cells at submicromolar concentrations. The reduction of the mitochondrial membrane potential, the induction of DNA fragmentation, and the activation of caspases-9 and -3 reveal that programmed cell death occurs through the intrinsic mitochondrial pathway. From the lipophilic and cationic nature of the osmacycle, in addition to a low oxidation potential (E-1/2=+0.27 V vs. Fc/Fc(+), Fc = ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis.

• 出版日期2010-7-26
• 单位厦门大学; 南阳理工学院