Lysosomal Targeted Cyclometallic Iridium(Ⅲ) Salicylaldehyde-Coumarin Schiff Base Complexes and Anticancer Application

Ruixi Xu; Yuting Wu; Zhe Liu; Jinfeng Liu; Xicheng Liu

doi:10.3389/fchem.2022.906954

Lysosomal Targeted Cyclometallic Iridium(Ⅲ) Salicylaldehyde-Coumarin Schiff Base Complexes and Anticancer Application

Front Chem. 2022 May 10:10:906954. doi: 10.3389/fchem.2022.906954. eCollection 2022.

Authors

Ruixi Xu¹, Yuting Wu², Zhe Liu¹, Jinfeng Liu², Xicheng Liu¹

Affiliations

¹ Institute of Anticancer Agents Development and Theranostic Application, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, China.
² College of Life Sciences, Qufu Normal University, Qufu, China.

Abstract

Natural coumarin derivatives and cyclometallic iridium (Ⅲ) (Ir^Ⅲ) complexes have attracted much attention in the field of anticancer. In this study, six coumarin-modified cyclometallic Ir^Ⅲ salicylaldehyde Schiff base complexes ([(ppy)₂Ir(O^N)]/[(ppy-CHO)₂Ir(O^N)]) were designed and synthesized. Compared with coumarin and Ir^Ⅲ complex monomers, target complexes exhibited favorable cytotoxic activity toward A549 and BEAS-2B cells. These complexes could induce extensive apoptosis of A549 cell (late apoptosis), which was represented by the disturbance of cell cycle (G₁-phase) and the accumulation of intracellular reactive oxygen species, exhibiting an anticancer mechanism of oxidation. With the help of suitable fluorescence of these complexes, no conflict with the probes, confocal detection confirmed that complexes showed an energy-dependent cellular uptake mechanism and triggered lysosome-mediated apoptosis in A549 cell line. Above all, our findings reveal the design of a lysosomal targeting cyclometallic Ir^Ⅲ Schiff base complexes and provide a new idea for the design of integrated drugs for diagnosis and treatment.

Keywords: Iridium(Ⅲ) complexes; Schiff base; anticancer; coumarin; lysosomal targeted.