Design, synthesis and antitumor activity of phthalazine-1,4-dione-based menaquinone analogs
Design, synthesis and antitumor activity of phthalazine-1,4-dione-based menaquinone analogs
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DOI：
10.1016/j.bmcl.2021.128065
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发表时间：
2021-05-06
影响因子：
2.7
通讯作者：
Kagechika, Hiroyuki
中科院分区：
文献类型：
--
作者：
Fujii, Shinya;Miura, Takahiro;Kagechika, Hiroyuki
需要新的化疗药物来治疗肝细胞癌，而由1，4-萘醌核心和(聚)异戊二烯链组成的维生素K的同系物--孟喹酮是潜在的候选者。在本研究中，我们设计并合成了一系列基于杂氮-1，4-二酮的喹酮类似物。其中，与正常肝细胞相比，含有完整异戊二烯链的化合物对肝癌细胞株JHH7具有选择性的抗增殖活性。香叶基衍生物10具有亚微摩尔活性，有望成为抗癌药物的先导化合物。
New chemotherapeutics are needed to treat hepatocellular carcinoma (HCC), and menaquinones, homologs of vitamin K consisting of a 1,4-naphthoquinone core and a (poly)isoprene chain, are potential candidates. In this study, we designed and synthesized a series of phthalazine-1,4-dione-based menaquinone analogs. Among them, compounds bearing the intact isoprene chain exhibited selective antiproliferative activity towards HCC cell line JHH7, as compared with normal hepatocytes. The geranyl derivative 10 showed submicromolar potency, and might be a promising lead compound for anticancer agents.