Inagaki Ryuta, Ninomiya Masayuki, Tanaka Kaori, Koketsu Mamoru
Department of Materials Science and Technology, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan).
Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193 (Japan).
ChemMedChem. 2015 Aug;10(8):1413-23. doi: 10.1002/cmdc.201500189. Epub 2015 Jun 18.
Naphthoquinones are considered privileged structures for anticancer drug molecules. The Heck reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with 1-bromo-3-methyl-2-butene offered easy access to lapachol. Several naturally occurring linear and angular heterocyclic quinoids (α-lapachone, β-lapachone, dunnione, and related analogues) were prepared from lapachol. Furthermore, we demonstrated that the synthetic naphthoquinones inhibit cell proliferation in human leukemia HL-60 cells. In particular, angular-type derivatives were found to possess moderate cytotoxicity and to elevate the levels of intracellular glutathione disulfide (GSSG). Our work highlights the significant potential of naturally occurring angular-series naphthoquinones as antileukemic agents.
萘醌被认为是抗癌药物分子的优势结构。2-羟基-1,4-萘醌（紫铆因）与1-溴-3-甲基-2-丁烯的Heck反应为制备拉帕醇提供了简便方法。从拉帕醇制备了几种天然存在的线性和角型杂环醌类（α-拉帕醌、β-拉帕醌、邓尼酮及相关类似物）。此外，我们证明合成萘醌可抑制人白血病HL-60细胞的增殖。特别是，角型衍生物被发现具有中等细胞毒性，并能提高细胞内谷胱甘肽二硫化物（GSSG）的水平。我们的工作突出了天然存在的角型系列萘醌作为抗白血病药物的巨大潜力。
