Affiliation:
1. Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, P. R. China
2. MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, P. R. China
Abstract
Abstract
Hepatocellular carcinoma (HCC) poses a serious threat to people’s health worldwide. Artesunate (ART), one of the classical antimalarial drugs, has recently been shown to exert significant cytotoxicity in various cancers, but its bioavailability is low. Cyclometalated iridium(iii) complexes have emerged as a promising class of anticancer therapeutic agents. Herein, through conjugation of two of them, three novel Ir(iii)–ART conjugates, [Ir(C–N)2(bpy-ART)](PF6) (bpy = 2,2′-bipyridine, C–N = 2-phenylpyridine (ppy, Ir-ART-1), 2-(2-thienyl)pyridine (thpy, Ir-ART-2), and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-ART-3)) have been synthesized, and their potential as anti-HCC agents was evaluated. We demonstrate that Ir-ART-1–3 display higher cytotoxicity against HCC cell lines than normal liver cells, and they can especially locate to mitochondria of HepG2 cells and induce a series of mitochondria-mediated apoptosis events. Moreover, Ir-ART-1–3 can regulate the cell cycle and inhibit metastasis of HepG2 cells. Finally, in vivo antitumor evaluation also demonstrates the inhibitory activity of Ir-ART-1 on tumor growth. Taken together, these Ir(iii)–ART conjugates have the potential to become drug candidates for future anti-HCC treatments.
Funder
National Natural Science Foundation of China
Kunming University of Science and Technology
Publisher
Oxford University Press (OUP)
Subject
Metals and Alloys,Biochemistry,Biomaterials,Biophysics,Chemistry (miscellaneous)
Cited by
18 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献