Levodopa/dopamine analogs as inhibitors of DNA synthesis in human melanoma cells.
Levodopa/dopamine analogs as inhibitors of DNA synthesis in human melanoma cells.
复制标题
左旋多巴/多巴胺类似物作为人类黑色素瘤细胞 DNA 合成的抑制剂。
DOI：
10.1111/1523-1747.ep13076753
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Wick,MM
中科院分区：
文献类型：
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作者：
Wick,MM
具有邻二羟基苯部分并在结构上与左旋多巴和多巴胺相关的化合物似乎属于一类新的生物活性剂，能够抑制多种正常和恶性真核细胞中的DNA合成。它们的部分作用似乎是通过其作为有效还原剂的特性，从而干扰对细胞 DNA 合成至关重要的几种氧化还原反应。有趣的是，这些化合物随后可以转化为氧化形式或醌形式，它们是强大的亲电子试剂，并进一步破坏细胞代谢。后一种机制似乎解释了在黑色素产生细胞中观察到的相对增加的细胞毒性。除了为治疗晚期恶性黑色素瘤提供潜在的新药物外，这些化合物可能被证明是确定影响正常和恶性细胞 DNA 合成速率的因素的有价值的工具。
Compounds possessing the ortho-dihydroxybenzene moiety and structurally related to levodopa and dopamine appear to belong to a new class of biologically active agents that are capable of inhibiting DNA synthesis in a variety of normal and malignant eukaryotic cells. They appear to work in part through their properties as potent reducing agents, and thereby interfere with several redox reactions that are crucial to the synthesis of cellular DNA. Interestingly, the compounds can then be converted to their oxidized or quinone forms, which are powerful electrophiles, and further disrupt cellular metabolism. This latter mechanism appears to account for the relatively increased cytotoxicity observed in melanin-producing cells. In addition to providing potential new agents for the treatment of advanced malignant melanoma, these compounds might prove to be valuable tools in determining the factors that influence rates of DNA synthesis in normal and malignant cells.