The 1,4-naphthoquinone derivatives bearing 5,7-dimethoxyl moiety were designed, synthesized, and tested as the antitumor agents against five human cancer cell lines (A549, Hela, HepG2, NCI-H460 and HL-60). All the compounds are described herein for the first time. The structure-activity relationships indicated that the presence of chlorine atom at the 2-position was crucial for the antiproliferative activity. Further, the electrochemical properties of the representative compounds (7e, 8e and 9e) were evaluated and a definite correlation between the redox potential and the antiproliferative activity. The most potent compound 9e displayed significant anti-leukemic activity with IC₅₀ value of 3.8 μM in HL-60 cells and weak cytotoxicity with IC₅₀ of 40.7 μM in normal cells WI-38. In mechanistic study for 9e, the increased numbers of apoptotic cells and increased cell population at G2/M phase correlated with ROS generation. Together, our results suggested that the derivatives of 2-chlorine-1,4-naphthoquinone might be the promising candidates for the treatment of promyelocytic leukemia.

设计，合成和测试带有5，7-二甲氧基部分的1，4-萘醌衍生物作为针对五种人类癌细胞系（A549，Hela，HepG2，NCI-H460和HL-60）的抗肿瘤剂。本文首次描述了所有化合物。构效关系表明2-位氯原子的存在对于抗增殖活性至关重要。此外，评价了代表性化合物（7e，8e和9e）的电化学性质，并且在氧化还原电势和抗增殖活性之间存在明确的相关性。最有效的化合物9e具有IC _50的显着抗白血病活性HL-60细胞的3.8μM值和弱的细胞毒性，正常细胞WI-38的IC ₅₀为40.7μM。在9e的机理研究中，G2 / M期凋亡细胞数量的增加和细胞数量的增加与ROS的产生有关。总之，我们的结果表明2-氯-1,4-萘醌的衍生物可能是治疗早幼粒细胞白血病的有希望的候选者。