Target ROS to induce apoptosis and cell cycle arrest by 5, 7-dimethoxy-1, 4-naphthoquinone derivative. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Li, Kun; Wang, Baitao; Zheng, Lifang; Yang, Kun; Li, Yuanyuan; Hu, Minmin; He, Dian
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 3(2018)
• Page Start: 273
• Page End: 277
• Publication Date: 2018-02-01
• Subjects: 1, 4-Naphthoquinone -- Anticancer agent -- Promyelocytic leukemia -- Apoptosis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.059
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Highlights: 5, 7-dimethoxy-1, 4-naphthoquinone derivatives were synthesized as antitumor agents. The cytotoxicity was evaluated against five tumor cell lines. The most potent compound9e exhibited selective cytotoxicity against HL-60 cells. 9e trigged ROS overproduction in HL-60 cells. 9e induced apoptosis and cell cycle arrest in G2/M by the ROS-dependent manner. Abstract: 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 and9e ) were evaluated and a definite correlation between the redox potential and the antiproliferative activity. The most potent compound9e 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 for9e, 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.