Oxovanadium complexes with quinoline and pyridinone ligands: Syntheses of the complexes and effect of alkyl chains on their apoptosis-inducing activity in leukemia cells

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• 作者：Tomoko Yamaguchi^a ; Shinya Watanabe^b ; Yuriko Matsumura^a ; Yoshikazu Tokuoka^b ; Akihiro Yokoyama^a ; ^{ayokoyama@st.seikei.ac.jp}
• 关键词：Vanadium ; Apoptosis ; Quinoline ; Pyridinone ; Caspase
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 May, 2012
• 卷：20
• 期：9
• 页码：3058-3064
• 文件大小：479 K

摘要

Vanadium complexes with quinoline ligands (1b-g) and pyridinone ligands (2b-d) were synthesized, and the effect of the length and shape of alkyl chains on the antiproliferative activity toward U937 cells was studied. For the synthesis of the vanadium complexes, quinoline and pyridinone ligands were prepared and then treated with VOSO₄ or VO(acac)₂. The vanadyl(IV) complexes were characterized by IR, ESR, and UV-vis spectroscopy and elemental analyses. The antiproliferative activity of 1a-g toward U937 cells showed little dependence on the length and shape of the alkyl chain. In contrast, a good correlation was found between the IC₅₀ values and partition coefficients (log P) values of 2a-c. Among them, 2c showed the highest inhibitory activity, and its IC₅₀ value was smaller than that of cisplatin. The apoptosis-inducing ability of 2b and 2c was supported by annexin V-propidium iodide staining experiments and agarose gel electrophoresis analysis. Inhibitors of caspase-3, -8, and -9 did not affect the antiproliferative activity of 2c, indicating that the apoptosis induced by 2c was via a caspase-independent pathway.