AUTHOR=Ma Xiurong , Lu Junjian , Yang Peixin , Huang Bo , Li Rongtao , Ye Ruirong 

TITLE=Synthesis, Characterization and Antitumor Mechanism Investigation of Heterometallic Ru(Ⅱ)-Re(Ⅰ) Complexes

JOURNAL=Frontiers in Chemistry

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.890925

DOI=10.3389/fchem.2022.890925

ISSN=2296-2646

ABSTRACT=<p>The development of heteronuclear metal complexes as potent anticancer agents has received increasing attention in recent years. In this study, two new heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes, [Ru(bpy)<sub>2</sub>LRe(CO)<sub>3</sub>(DIP)](PF<sub>6</sub>)<sub>3</sub> and [Ru(phen)<sub>2</sub>LRe(CO)<sub>3</sub>(DIP)](PF<sub>6</sub>)<sub>3</sub> [<bold>RuRe-1</bold> and <bold>RuRe-2</bold>, L = 2-(4-pyridinyl)imidazolio[4,5-f][1,10]phenanthroline, bpy = 2,2′-bipyridine, DIP = 4,7-diphenyl-1,10-phenanthroline, phen = 1,10-phenanthroline], were synthesized and characterized. Cytotoxicity assay shows that <bold>RuRe-1</bold> and <bold>RuRe-2</bold> exhibit higher anticancer activity than cisplatin, and exist certain selectivity toward human cancer cells over normal cells. The anticancer mechanistic studies reveal that <bold>RuRe-1</bold> and <bold>RuRe-2</bold> can induce apoptosis through the regulation of cell cycle, depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS), and caspase cascade. Moreover, <bold>RuRe-1</bold> and <bold>RuRe-2</bold> can effectively inhibit cell migration and colony formation. Taken together, heteronuclear Ru(Ⅱ)-Re(Ⅰ) metal complexes possess the prospect of developing new anticancer agents with high efficacy.</p>