6-Substituted 1,4-naphthoquinone oxime derivatives (I): synthesis and evaluation of their cytotoxic activity

• Published in: Monatshefte für Chemie Vol. 148; no. 6; pp. 1011 - 1023
• Main Authors: Huang, Guang, Zhao, Hui-ran, Zhou, Wen, Dong, Jin-yun, Zhang, Qi-jing, Meng, Qing-qing, Zhu, Bao-quan, Li, Shao-shun
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.06.2017; Springer Nature; Springer Nature B.V
• Subjects: Analytical Chemistry; Anticancer properties; Chemistry; Chemistry and Materials Science; Chemistry, Multidisciplinary; Chemistry/Food Science; Inorganic Chemistry; Organic Chemistry; Original Paper; Physical Chemistry; Physical Sciences; Science & Technology; Theoretical and Computational Chemistry; Cytotoxicity; Aromatization; Anticancer agents; Naphthoquinone; Structure–activity relationship; SHIKONIN; Structure-activity relationship; ANTITUMOR-ACTIVITY; ALKANNIN
• ISSN: 0026-9247; 1434-4475
• DOI: 10.1007/s00706-016-1899-z

A series of 6-substituted 1,4-naphthoquinone oxime derivatives were synthesized and evaluated for their in vitro cytotoxicity against four cancer cell lines and one normal cell line. Some compounds exhibited moderate to good cytotoxicity towards cancer cells and meanwhile all the synthesized compounds displayed no apparent cytotoxic activity against normal cells (IC 50  > 100 μM). Among these oxime derivatives, three compounds showed more potent cytotoxicity against human colon cancer cell lines (HCT-15) than adriamycin and 5-fluorouracil, with an IC 50 value of 2.52, 1.96, and 2.27 μM, respectively. Additionally, structure–activity relationship studies revealed that cytotoxic effects of these oxime derivatives were not only largely dependent upon the size of alkyl chain R 1 , but also upon substituents R 2 of the branch chain, indicating that the strong cytotoxicity of these compounds was ascribed to their appropriate lipophilicity. Collectively, this study could provide available strategy for design and synthesis of 6-substituted 1,4-naphthoquinone oxime derivatives as potential anticancer agents. Graphical abstract