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

In this study, 13 transition metal complexes, namely, [Cu((LH)-H-1)(H2O)(2)]center dot(H2O)center dot NO3 (1), [Cu ((LH2)-H-n)(2)center dot(NO3)center dot(H2O)(2) (2, n = 2; 3, n = 3; 4, n = 4; 5, n = 5), [Co((LH)-H-n)(2)](2)center dot(H2O)(0.5) (6, n = 2; 7, n = 3; 8, n = 4; 9, n = 5), [Cu((LH)-H-6)(0.5)((LH)-H-10)(0.5)(phen)]center dot(CH3OH)(0.25) (10), [CU((LH)-H-11) (phen)](4)center dot(H2O)(9) (11), [Cu((LH)-H-8)(0.27)((LH)-H-12)(0.73)(phen)](4)center dot(H2O)(5.5)(CH3OH) (12), and [Cu((LH)-H-9) (phen)](3)center dot(H2O)(7)center dot(CH3OH) (13), were synthesized using Schiff base ligands and characterized by elemental analysis (EA), infrared spectroscopy OR), 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 mu M), with differences greater than one order of magnitude. Moreover, complexes 11 and 13 could induce apoptosis and autophagy in A549/DDP cells via the mitochondria! dysfunction pathway that affects the regulation of autophagy- and mitochondrial-related proteins. Importantly, the results indicate that the two novel salicy'aldehyde Schiff base analogs, 11 and 13, exhibited pronounced and selective activity against A549/DDP xenografts in vivo.

Automated summary

In this study, 13 transition metal complexes were synthesized and characterized. Two novel complexes exhibited strong cytotoxic activities against A549/DDP cancer cells, inducing apoptosis and autophagy via the mitochondria! dysfunction pathway. These complexes also showed pronounced and selective activity against A549/DDP xenografts in vivo.