PUBLICATION

Evaluation of the Anticancer Activities of Novel Transition Metal Complexes with Berenil and Nitroimidazole

Authors
Czarnomysy, R., Radomska, D., Muszyńska, A., Hermanowicz, J.M., Prokop, I., Bielawska, A., Bielawski, K.
ID
ZDB-PUB-210305-14
Date
2020
Source
Molecules   25(12): (Journal)
Registered Authors
Keywords
anticancer compounds, breast cancer, multi-factorial compounds, nitroimidazole, transition metal complexes
MeSH Terms
  • Xenograft Model Antitumor Assays
  • Coordination Complexes/chemical synthesis
  • Coordination Complexes/chemistry
  • Coordination Complexes/pharmacology*
  • Platinum/pharmacology
  • Humans
  • Autophagosomes/drug effects*
  • Zebrafish
  • Cisplatin/pharmacology
  • Cell Line, Tumor
  • Membrane Potential, Mitochondrial/drug effects
  • Organometallic Compounds/pharmacology*
  • Antineoplastic Agents/pharmacology*
  • Transition Elements/chemistry
  • Nitroimidazoles/chemistry*
  • Female
  • Cell Survival/drug effects
  • Mitochondria/drug effects
  • Mitochondria/metabolism
  • Diminazene/analogs & derivatives*
  • Diminazene/chemistry
  • Breast Neoplasms/drug therapy*
  • Apoptosis/drug effects
  • Apoptosis/genetics
  • DNA/drug effects
  • DNA/metabolism
  • DNA Topoisomerases, Type II/metabolism
  • Gold/pharmacology
  • Animals
  • Palladium/pharmacology
PubMed
32575817 Full text @ Molecules
Abstract
Novel transition metal complexes (Au, Pd, Pt) with berenil and 2-(1-methyl-5-nitroimidazol-2-yl)ethanol were obtained through two-step synthesis. The cytotoxicity assay against MCF-7 and MDA-MB-231 breast cancer cells revealed that novel platinum and palladium complexes cause a reduction on the viability of MCF-7 and MDA-MB-231 breast cancer cells to a greater extent than cisplatin. The complexes showed lower cytotoxicity on normal MCF-10A human breast epithelial cells than on tumor cells. Furthermore, we observed that these complexes selectively concentrate in tumor cell mitochondria due to the characteristic for these cells increased membrane potential that may explain their increased proapoptotic activity. The activity of the synthesized compounds against topoisomerase type IIα and their increased impact on DNA defragmentation also were documented. The novel complexes also induced autophagosome changes and inhibited tumor growth in xenograft models (established using breast cancer cells).
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