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 and .

In this study, 13 transition metal complexes, namely, [Cu(LH)(HO)]·(HO)·NO (1), [Cu(LH)]·(NO)·(HO) (2, = 2; 3, = 3; 4, = 4; 5, = 5), [Co(LH)]·(HO) (6, = 2; 7, = 3; 8, = 4; 9, = 5), [Cu(LH)(LH)(phen)]·(CHOH) (10), [Cu(LH) (phen)]·(HO) (11), [Cu(LH)(LH)(phen)]·(HO)(CHOH) (12), and [Cu(LH) (phen)]·(HO)·(CHOH) (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 = 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 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 .