National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei 112, Taiwan, ROC.
School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, ROC.
Bioorg Med Chem Lett. 2021 Jun 1;41:127976. doi: 10.1016/j.bmcl.2021.127976. Epub 2021 Mar 22.
A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC = 1.39 µM). Some compounds were evaluated for DNA topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed topoisomerase inhibition activity with IC values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.
一系列的 1,4-萘醌衍生物的洛索酚（1），6-羟基-1,4-萘醌（2），和胡桃醌（3）是通过烷基化，酰化和磺化反应合成的。洛索酚衍生物 1a-1k（A型），6-羟基-1,4-萘醌衍生物 2a-2j（B 型），和胡桃醌衍生物 3a-3h（C 型）的产率分别为 52-99％，53-96％和 28-95％。所有化合物均在体外进行了人口腔表皮样癌细胞（KB）和宫颈上皮样癌细胞（HeLa）的细胞毒性测试，并研究了它们的构效关系。化合物 3c 在 KB 细胞系中表现出最强的活性（IC = 1.39 μM）。一些化合物还评估了 DNA 拓扑异构酶 I 抑制活性。化合物 2c、3、3a 和 3d 对拓扑异构酶具有抑制活性，IC 值为 8.3-91 μM。通过循环伏安法测定了所有萘醌在磷酸盐缓冲液中的标准氧化还原电位（E°）。在 pH 7.2 的磷酸盐缓冲液中，所有萘醌的标准氧化还原电位（E°）通过循环伏安法进行了测定。发现 A 型化合物的氧化还原电位与抑制作用之间存在明确的相关性。
