Cytotoxic activity, albumin and DNA binding of new copper(II) complexes with chalcone-derived thiosemicarbazones

Abstract

[Cu(HL)Cl2] complexes of chalcone-derived thiosemicarbazones were obtained with 3-phenyl-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCTPh), complex (1), 3-(4-chlorophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4ClPh), complex (2), 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4BrPh), complex (3), and 3-(4-nitrophenyl-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone (HPyCT4NO2Ph), complex (4). 1-3 showed interaction with bovine serum albumin (BSA) and deoxyribonucleic acid from calf thymus (CT-DNA). The cytotoxic activities of the thiosemicarbazones and complexes (1-4) were tested against HL60 (wild type human promyelocytic leukemia), Jurkat (human immortalized line of T lymphocyte), MDA-MB 231 (human breast carcinoma) and HCT-116 (human colorectal carcinoma) tumor cell lineages. Upon coordination to copper(II) cytotoxicity significantly increased in Jurkat, MDA-MB 231 and HCT-116 cells. Unlike the free thiosemicarbazones, 1-4 induced DNA fragmentation in solid tumor cells indicating their pro-apoptotic potential.

Keywords: Apoptosis; Chalcones; Copper(II) complexes; Cytotoxic activity; Interaction with DNA; Interaction with albumin; Thiosemicarbazones.