Unusual eta2-allene osmacycle with apoptotic properties.
Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in HeLa cells led to the discovery of a highly cytotoxic eta2-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 (E1/2=+0.27 V vs. Fc/Fc+, Fc=ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis.
He
Xumin
X
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
Gong
Lei
L
Kräling
Katja
K
Gründler
Katharina
K
Frias
Corazon
C
Webster
Richard D
RD
Meggers
Eric
E
Prokop
Aram
A
Xia
Haiping
H
D000466:Alkadienes / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009942:Organometallic Compounds
D000466:Alkadienes; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C025947:propadiene; D020169:Caspases