1. Discovery of thirteen cobalt(II) and copper(II) salicylaldehyde Schiff base complexes that induce apoptosis and autophagy in human lung adenocarcinoma A549/DDP cells and that can overcome cisplatin resistance in vitro and in vivo .
- Author
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Chen YT, Zhang SN, Wang ZF, Wei QM, and Zhang SH
- Subjects
- A549 Cells, Adenocarcinoma, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Autophagy drug effects, Cisplatin pharmacology, Coordination Complexes chemistry, Drug Resistance, Neoplasm, Humans, Lung Neoplasms, Models, Molecular, Molecular Structure, Aldehydes chemistry, Apoptosis drug effects, Cobalt chemistry, Coordination Complexes pharmacology, Copper chemistry
- Abstract
In this study, 13 transition metal complexes, namely, [Cu(L
1 H)(H2 O)2 ]·(H2 O)·NO3 (1), [Cu(Ln H2 )2 ]·(NO3 )·(H2 O)2 (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co(Ln H)2 ]2 ·(H2 O)0.5 (6, n = 2; 7, n = 3; 8, n = 4; 9, n = 5), [Cu(L6 H)0.5 (L10 H)0.5 (phen)]·(CH3 OH)0.25 (10), [Cu(L11 H) (phen)]4 ·(H2 O)9 (11), [Cu(L8 H)0.27 (L12 H)0.73 (phen)]4 ·(H2 O)5.5 (CH3 OH) (12), and [Cu(L9 H) (phen)]3 ·(H2 O)7 ·(CH3 OH) (13), were synthesized using Schiff base ligands and characterized by elemental analysis (EA), infrared spectroscopy (IR), and single-crystal X-ray diffraction (SC-XRD). Compared with complexes 1-9, complexes 10-13 displayed stronger cytotoxic activities against the tested A549/DDP cancer cells (IC50 = 0.97-3.31 μM), with differences greater than one order of magnitude. Moreover, complexes 11 and 13 could induce apoptosis and autophagy in A549/DDP cells via the mitochondrial dysfunction pathway that affects the regulation of autophagy- and mitochondrial-related proteins. Importantly, the results indicate that the two novel salicylaldehyde Schiff base analogs, 11 and 13, exhibited pronounced and selective activity against A549/DDP xenografts in vivo .- Published
- 2022
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