Folic acid-conjugated mixed-ligand copper (II) complexes as promising cytotoxic agents for triple-negative breast cancers: A case study using MDA-MB-231 cell

摘要: The new mixed-ligand copper(II) complexes [Cu(FAA)(diimine)(H2O)](ClO4)2 (1–4) [FAA is folic acid-conjugated ethyl pyridyl amine; diimine is 1,10-phenanthroline (phen; 1), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp; 2), 3,4,7,8-tetramethyl-1,10-phenanthroline (3,4,7,8-tmp; 3), and dipyrido-[3,2-f:2′,3′-h]-quinoxaline (dpq; 4)] were synthesized and characterized adopting appropriate analytical and spectroscopic techniques. DNA and protein binding studies showed that the complex [Cu(FAA)(5,6-dmp)(H2O)]2+ (2) has higher DNA- and protein-binding abilities than the other complexes. In the presence of the activating agent ascorbic acid, the same complex 2 caused pronounced DNA cleavage. The mechanistic study revealed that the oxidative DNA cleavage induced by complex 2 was effected through the freely diffusible hydroxyl radical; the same complex induced the highest incidence of cytotoxicity in the …