Fluorescent iridium(iii) coumarin-salicylaldehyde Schiff base compounds as lysosome-targeted antitumor agents

Abstract

Fluorescent iridium(iii) coumarin-salicylaldehyde Schiff base antitumor compounds change the ROS and ΔΨm, induce lysosomal damage, and lead to apoptosis.

Highly Efficient Ir(III)‐Coumarin Photo‐Redox Catalyst for Synergetic Multi‐Mode Cancer Photo‐Therapy

“…The intracellular localization of anticancer agents controls the MOA significantly [56] . In recent years, anticancer agents with selective localization in a particular cellular organelle (other than cell nucleus) have attracted significant attention [23,24,43,44,57,58] . Such molecules may have the potential to overcome the drug resistance problem of platins [57] .…”

“…The ability of the complexes to induce 1 O 2 generation and photo-oxidation of NAD(P)H on 465 nm and 525 nm light irradiation inspired us to explore the possibility of the complexes as PDT agents. MTT assay [42][43][44] was used to investigate the dark-and photo-cytotoxicity of Ir1-Ir4 against human cervical cancer cell line (HeLa), epidermoid carcinoma cell line (A431), human nasopharyngeal epithelial cell line (NP69) and mouse melanoma cell line (B16). The clinical chemotherapy drug cisplatin and PDT drug 5-aminolevulinic acid (5-ALA) were used as positive controls for the dark-and photo-therapy experiments, respectively.…”

“…[56] In recent years, anticancer agents with selective localization in a particular cellular organelle (other than cell nucleus) have attracted significant attention. [23,24,43,44,57,58] Such molecules may have the potential to overcome the drug resistance problem of platins. [57] To study the intracellular localization of our complexes, we used mitotracker deep-red and lysotracker red to stain the mitochon-dria and lysosomes, respectively.…”

In Vitro and In Vivo of Triphenylamine-Appended Fluorescent Half-Sandwich Iridium(III) Thiosemicarbazones Antitumor Complexes

“…Meanwhile, these complexes also exhibit similar or better anticancer activity and selectivity than the reported traditional half-sandwiched structrue Ir III complex (usually depicted as [(η 5 -Cp*)­Ir­(L ∧ L)­Cl]­PF 6 , L ∧ L = N ∧ C, N ∧ O, N ∧ N, N ∧ S, etc., Table S3). ,,, …”

“…Lysosomes are acidic membrane-bound vesicles (containing more than 50 hydrolytic enzymes), which can act upon a variety of biological macromolecules and lead to some irreversible cellular processes such as the extracellular release of active enzymes, the inhibition of cell migration and metabolism, extensive apoptosis, etc. − Compared with normal cells, tumor cells contain more lysosomes, and show higher cathepsin activity . Studies indicate that the introduction of heteroatoms containing lone electron pairs to peripheral ligands have achieved ideal results in lysosomal targeting and real-time drug tracking. , However, there is a major drawback for the classical half-sandwiched Ir III complexes: generally no suitable fluorescence, which makes them difficult to detect targeted location and metabolic circulation in tissues.…”