Platinum(II) chloride indenyl complexes: electrochemical and biological evaluation

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作者
Lisa Dalla Via
Saverio Santi
Vito Di Noto
Alfonso Venzo
Enzo Agostinelli
Annarica Calcabrini
Maria Condello
Antonio Toninello
机构
[1] University of Padova,Department of Pharmaceutical Sciences
[2] University of Padova,Department of Chemical Sciences
[3] Institute of Molecular Sciences and Technologies,CNR
[4] University of Rome “La Sapienza” and CNR,ISTM
[5] Italian National Institute of Health,Department of Biochemical Sciences, Institute of Molecular Biology and Pathology
[6] University of Padova,Department of Technology and Health
关键词
Platinum(II) complexes; Indenyl electrochemistry; Antiproliferative activity; DNA binding; Mitochondrial permeability transition;
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摘要
Four platinum(II) complexes of general formula [PtCl(η1-C9H7)L2] [where L2 is 1,2-bis(diphenylphosphino)ethane (dppe) 1 or cycloocta-1,5-diene (cod) 3] and [PtCl2L2] (where L2 is dppe 2 or cod 4) were studied. Inhibition growth assays on human tumor cell lines evidenced for 1 and 3 an antiproliferative effect and, interestingly, the cytotoxic effect exerted by 1 is similar to that of cisplatin. Electrochemical and NMR measurements allowed us to determine the structural and redox properties. Investigation of the mechanism of action responsible for the cytotoxicity demonstrated a weak capacity of interacting with DNA. Some experiments performed on rat liver mitochondria indicate that 1 acts as an inducer of the mitochondrial permeability transition, thus leading to the release of proapoptotic factors, such as cytochrome c and apoptosis-inducing factor.
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