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一种天然生物碱椭圆体的新型结构衍生物 MDPSQ,可诱导白血病细胞坏死。

A novel structural derivative of natural alkaloid ellipticine, MDPSQ, induces necrosis in leukemic cells.

机构信息

Department of Biochemistry, Indian Institute of Science, Bangalore, 560 012, India.

出版信息

Invest New Drugs. 2011 Aug;29(4):523-33. doi: 10.1007/s10637-009-9379-5. Epub 2010 Jan 13.

Abstract

DNA intercalating molecules are promising chemotherapeutic agents. In the present study, a novel DNA intercalating compound of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having 8-methyl-4-(3 diethylaminopropylamino) side chain is studied for its chemotherapeutic properties. Our results showed that 8-methyl-4-(3 diethylaminopropylamino) pyrimido [4',5':4,5] selenolo(2,3-b)quinoline (MDPSQ) induces cytotoxicity in a time- and concentration-dependent manner on leukemic cell lines. Both cell cycle analysis and tritiated thymidine assays revealed that MDPSQ affects DNA replication. Treatment with MDPSQ resulted in both elevated levels of DNA strand breaks and repair proteins, further indicating its cytotoxic effects. Besides, Annexin V/PI staining revealed that MDPSQ induces cell death by triggering necrosis rather than apoptosis.

摘要

DNA 插入分子是很有前途的化疗药物。在本研究中,研究了具有 8-甲基-4-(3-二乙氨基丙基氨基)侧链的嘧啶并[4',5':4,5]硒咯[2,3-b]喹啉系列的新型 DNA 插入化合物,以研究其化疗特性。我们的结果表明,8-甲基-4-(3-二乙氨基丙基氨基)嘧啶并[4',5':4,5]硒咯[2,3-b]喹啉(MDPSQ)以时间和浓度依赖的方式诱导白血病细胞系的细胞毒性。细胞周期分析和氚标记胸腺嘧啶测定均表明 MDPSQ 影响 DNA 复制。用 MDPSQ 处理会导致 DNA 链断裂和修复蛋白水平升高,进一步表明其细胞毒性作用。此外,Annexin V/PI 染色显示 MDPSQ 通过引发坏死而不是凋亡诱导细胞死亡。

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