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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 51; no. 10; pp. 4068 - 4078
• Main Authors: Chen, Ya-Ting, Zhang, Shao-Nan, Wang, Zhen-Feng, Wei, Qing-Min, Zhang, Shu-Hua
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 08.03.2022
• Subjects: A549 Cells; Adenocarcinoma; Aldehydes - chemistry; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Chemical analysis; Cisplatin - pharmacology; Cobalt - chemistry; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Coordination compounds; Copper; Copper - chemistry; Crystals; Drug Resistance, Neoplasm; Humans; Imines; In vivo methods and tests; Infrared analysis; Infrared spectroscopy; Lung Neoplasms; Models, Molecular; Molecular Structure; Single crystals; Transition metal compounds; Xenotransplantation
• ISSN: 1477-9226; 1477-9234; 1477-9234
• DOI: 10.1039/D1DT03749H

In this study, 13 transition metal complexes, namely, [Cu(L 1 H)(H 2 O) 2 ]·(H 2 O)·NO 3 (1), [Cu(L n H 2 ) 2 ]·(NO 3 )·(H 2 O) 2 (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co(L n H) 2 ] 2 ·(H 2 O) 0.5 (6, n = 2; 7, n = 3; 8, n = 4; 9, n = 5), [Cu(L 6 H) 0.5 (L 10 H) 0.5 (phen)]·(CH 3 OH) 0.25 (10), [Cu(L 11 H) (phen)] 4 ·(H 2 O) 9 (11), [Cu(L 8 H) 0.27 (L 12 H) 0.73 (phen)] 4 ·(H 2 O) 5.5 (CH 3 OH) (12), and [Cu(L 9 H) (phen)] 3 ·(H 2 O) 7 ·(CH 3 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 (IC 50 = 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 .