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Insights into the antineoplastic activity and mechanisms of action of coumarin-coordinated 8-hydroxyquinoline ruthenium(II/III) compounds.
Du, Ling-Qi; Yang, Yan; Ruan, Li; Sun, Song; Mo, Dong-Yin; Cai, Jin-Yuan; Liang, Hong; Shu, Sai; Qin, Qi-Pin.
Afiliação
  • Du LQ; Guangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, China.
  • Yang Y; Guangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, China; School of food and chemical engineering, Liuzhou Institute of Technology, Liuzhou, Guangxi 545000, China.
  • Ruan L; Guangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, China.
  • Sun S; School of food and chemical engineering, Liuzhou Institute of Technology, Liuzhou, Guangxi 545000, China.
  • Mo DY; Guangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, China.
  • Cai JY; School of food and chemical engineering, Liuzhou Institute of Technology, Liuzhou, Guangxi 545000, China. Electronic address: jingyuan025163@163.com.
  • Liang H; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China.
  • Shu S; School of food and chemical engineering, Liuzhou Institute of Technology, Liuzhou, Guangxi 545000, China.
  • Qin QP; Guangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, 1303 Jiaoyudong Road, Yulin 537000, China; State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and P
J Inorg Biochem ; 259: 112659, 2024 Oct.
Article em En | MEDLINE | ID: mdl-38976937
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., [RuII2(µ2-Cl)2(QL1a)2(DMSO)4] (YNU-4a = Yulin Normal University-4a), [RuII2(µ2-Cl)2(QL1b)2(DMSO)4] (YNU-4b), [RuII2(µ2-Cl)2(QL1c)2(DMSO)4] (YNU-4c), [RuII2(µ2-Cl)2(QL1d)2(DMSO)4]⋅2CH3OH (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), [RuIICl2(H-QL3a)2(DMSO)2] (YNU-4i), [RuIICl2(H-QL3b)2(DMSO)2] (YNU-4j), and [RuIICl2(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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rutênio / Oxiquinolina / Cumarínicos / Complexos de Coordenação / Antineoplásicos Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rutênio / Oxiquinolina / Cumarínicos / Complexos de Coordenação / Antineoplásicos Idioma: En Ano de publicação: 2024 Tipo de documento: Article