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

Eur J Med Chem. 2013 Jul:65:415-26. doi: 10.1016/j.ejmech.2013.04.036. Epub 2013 May 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Binding Sites / drug effects
  • Cattle
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chalcone / chemistry*
  • Copper / chemistry*
  • DNA / chemistry
  • DNA / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • HL-60 Cells
  • Humans
  • Jurkat Cells
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Serum Albumin, Bovine / antagonists & inhibitors*
  • Serum Albumin, Bovine / chemistry
  • Structure-Activity Relationship
  • Thiosemicarbazones / chemistry*

Substances

  • Antineoplastic Agents
  • Organometallic Compounds
  • Thiosemicarbazones
  • Serum Albumin, Bovine
  • Chalcone
  • Copper
  • DNA
  • calf thymus DNA