Synthesis and biological evaluation of novel asymmetric naphthalene diimide derivatives as anticancer agents depending on ROS generation

Xiaojuan Xu; Senzhen Wang; Yuan Chang; Chaochao Ge; Xinna Li; Yongli Feng; Songqiang Xie; Chaojie Wang; Fujun Dai; Wen Luo

doi:10.1039/c8md00265g

Synthesis and biological evaluation of novel asymmetric naphthalene diimide derivatives as anticancer agents depending on ROS generation

Medchemcomm. 2018 Jul 6;9(8):1377-1385. doi: 10.1039/c8md00265g. eCollection 2018 Aug 1.

Authors

Xiaojuan Xu^{1

2}, Senzhen Wang¹, Yuan Chang¹, Chaochao Ge¹, Xinna Li¹, Yongli Feng¹, Songqiang Xie³, Chaojie Wang¹, Fujun Dai¹, Wen Luo¹

Affiliations

¹ Key Lab of Natural Medicine and Immune Engineering , Henan University , Kaifeng 475004 , China . Email: fjdwl@hotmail.com ; Email: luowen83@henu.edu.cn.
² Pharmaceutical College , Henan University , Kaifeng 475004 , China.
³ Institute of Chemical Biology , Henan University , Kaifeng 475004 , China.

Abstract

Naphthalenetetracarboxylic diimide (NDI) is widely used as a photoelectric material in the field of medicine. A series of asymmetric naphthalene diimide derivatives were synthesized and evaluated for their anticancer properties by various experimental assays. As the representative compound, 3c exerted significantly greater inhibitory effects on hepatoma cells SMMC-7721 and Hep G2 with an IC₅₀ value of 1.48 ± 0.43 μM and 1.70 ± 0.53 μM, respectively, than normal hepatocytes QSG-7701 with an IC₅₀ value of 7.11 ± 0.08 μM. Treatment with compound 3c (3 μM) for 48 h resulted in apoptosis of SMMC-7721 cells and Hep G2 cells with 52.1% and 67.8% apoptotic cells, respectively. Compound 3c induced autophagy and suppressed the migration of hepatoma cells in a concentration-dependent manner, resulting from the generation of reactive oxygen species (ROS). Based on its biological ability, compound 3c was considered as a potent anticancer agent.