1. Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds.
- Author
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Du LQ, Yang Y, Ruan L, Sun S, Mo DY, Cai JY, Liang H, Shu S, and Qin QP
- Subjects
- Humans, Cell Line, Tumor, Animals, Apoptosis drug effects, Mice, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Ruthenium chemistry, Coordination Complexes pharmacology, Coordination Complexes chemistry, Coordination Complexes chemical synthesis, Coumarins chemistry, Coumarins pharmacology, Oxyquinoline chemistry, Oxyquinoline pharmacology
- Abstract
Ruthenium(II/III) coordination compounds have gained widespread attention as chemotherapy drugs, photosensitizers, and photodynamic therapy reagents. Herein, a family of 11 novel coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds, i.e., [Ru
II 2 (μ2 -Cl)2 (QL1a)2 (DMSO)4 ] (YNU-4a = Yulin Normal University-4a), [RuII 2 (μ2 -Cl)2 (QL1b)2 (DMSO)4 ] (YNU-4b), [RuII 2 (μ2 -Cl)2 (QL1c)2 (DMSO)4 ] (YNU-4c), [RuII 2 (μ2 -Cl)2 (QL1d)2 (DMSO)4 ]⋅2CH3 OH (YNU-4d), [RuII (QL1e)2 (DMSO)2 ] (YNU-4e), [RuIII (QL1e)2 (QL3a)] (YNU-4f), [RuIII (QL1e)2 (QL3b)] (YNU-4g), [RuIII (QL1e)2 (QL3c)] (YNU-4h), [RuII Cl2 (H-QL3a)2 (DMSO)2 ] (YNU-4i), [RuII Cl2 (H-QL3b)2 (DMSO)2 ] (YNU-4j), and [RuII Cl2 (H-QL3c)2 (DMSO)2 ] (YNU-4k), featuring the coligands 5,7-diiodo-8-hydroxyquinoline (H-QL1a), 5,7-dichloro-8-quinolinol (H-QL1b), 5-chloro-7-iodo-8-hydroxyquinolin (H-QL1c), 5,7-dibromo-8-hydroxyquinoline (H-QL1d), and 5,7-dichloro-8-hydroxy-2-methylquinoline (H-QL1e) and the main ligands 6,7-dichloro-3-pyridin-2-yl-chromen-2-one (H-QL3a), 6-bromo-3-pyridin-2-yl-chromen-2-one (H-QL3b), and 6-chloro-3-pyridin-2-yl-chromen-2-one (H-QL3c), respectively. The structure of compounds YNU-4a-YNU-4k was fully confirmed by conducting various spectroscopic analyses. The anticancer activity of YNU-4a-YNU-4k was evaluated in cisplatin-resistant A549/DDP lung cancer cells (LC549) versus normal embryonic kidney (HEK293) cells. Notably, compound YNU-4f bearing QL1e and QL3a ligands showed a more pronounced antiproliferative effect against LC549 cells (IC50 = 1.75 ± 0.09 μM) with high intrinsic selectivity toward LC549 cancer cells than YNU-4a-YNU-4e, H-QL1a-H-QL1e, cisplatin (PDD), YNU-4g-YNU-4k, and H-QL3a-H-QL3c. Additionally, a colocalization assay analysis of YNU-4e and YNU-4f showed that these two ruthenium(II/III) compounds were subcellularly accumulated in the mitochondria and other regions of the cytoplasm, where they induce mitophagy, adenosine triphosphate (ATP) reduction, mitochondrial respiratory chain complex I/IV(RC1/RC4) inhibition, and mitochondrial dysfunction. Accordingly, compounds YNU-4a-YNU-4k can be regarded as mitophagy inductors for the eradication of cisplatin-resistant LC549 cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)- Published
- 2024
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