Time-Dependent Cytotoxic Properties of Terpyridine-Based Copper Complexes

Chembiochem. 2020 Aug 17;21(16):2348-2355. doi: 10.1002/cbic.202000154. Epub 2020 Apr 29.

Abstract

Five copper complexes supported by terpyridine ligands were prepared and characterized, viz. [Cu3 Cl4 (naphtpy)2 ][CuCl2 ] (1), [Cu2 Cl2 (naphtpy)2 ](ClO4 )2 (2), [CuCl2 (naphtpy)]2 (MeOH)3 (H2 O) (3), [CuCl2 (Cltpy)] (4) and [Cu(Cltpy)2 ](ClO4 )2 (5); (where naphtpy stands for 4'-((naphthalen-2-yl)methoxy)-2,2':6',2''-terpyridine and Cltpy for 4'-chloro-2,2':6',2''-terpyridine). Their ability to interact with DNA was investigated, and their cytotoxic behaviour was examined with three cells lines, namely human ovarian carcinoma cells (A2780), their derived cisplatin-resistant line (A2780cis), and human cervix adenocarcinoma cells (HeLa). All compounds show good cytotoxic properties (especially after 72 h of incubation). Remarkably, two compounds, 4 and 5, are still almost inactive after 24 h (particularly 4), but are highly active after 72 h, with IC50 values in the low-micromolar to sub-micromolar range. Compounds 1 and 2 induce necrosis, whereas late apoptosis is observed with 3-5, 4 exhibiting a behaviour close to that of cisplatin.

Keywords: antineoplastic agents; cell death; chemical nuclease; copper; oxidative cleavage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Coordination Complexes / chemistry*
  • Coordination Complexes / metabolism
  • Coordination Complexes / pharmacology*
  • Copper / chemistry*
  • DNA / chemistry
  • DNA / metabolism
  • Humans
  • Kinetics
  • Models, Molecular
  • Nucleic Acid Conformation
  • Pyridines / chemistry*

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Pyridines
  • Copper
  • DNA
  • pyridine