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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.

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In this study, 13 transition metal complexes, namely, [Cu(L1H)(H2O)2]·(H2O)·NO3 (1), [Cu(LnH2)2]·(NO3)·(H2O)2 (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co(LnH)2]2·(H2O)0.5 (6, n… Click to show full abstract

In this study, 13 transition metal complexes, namely, [Cu(L1H)(H2O)2]·(H2O)·NO3 (1), [Cu(LnH2)2]·(NO3)·(H2O)2 (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co(LnH)2]2·(H2O)0.5 (6, n = 2; 7, n = 3; 8, n = 4; 9, n = 5), [Cu(L6H)0.5(L10H)0.5(phen)]·(CH3OH)0.25 (10), [Cu(L11H) (phen)]4·(H2O)9 (11), [Cu(L8H)0.27(L12H)0.73(phen)]4·(H2O)5.5(CH3OH) (12), and [Cu(L9H) (phen)]3·(H2O)7·(CH3OH) (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.

Keywords: h2o; schiff base; a549 ddp

Journal Title: Dalton transactions
Year Published: 2022

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