Organotin complexes containing carboxylate ligands with maleimide and naphthalimide derived partial structures: TrxR inhibition, cytotoxicity and activity in resistant cancer cells

Eur J Med Chem. 2014 Nov 24:87:794-800. doi: 10.1016/j.ejmech.2014.09.075. Epub 2014 Sep 28.

Abstract

Di-n-butyltin(IV) carboxylate and tri-n-butyltin(IV) carboxylate derivatives have demonstrated strong cytotoxic effects in different types of tumor cells. Complexes with carboxylate ligands that contain maleimide and naphthalimide derived partial structures were synthesized, characterized and investigated for inhibition of the tumor-relevant enzyme thioredoxin reductase and antiproliferative effects in cancer cells. The complexes were moderate inhibitors of thioredoxin reductase with activities in the micromolar range and triggered strong cytotoxic effects in MCF-7 breast cancer and HT-29 colon carcinoma cells. Interestingly, selected complexes were highly active in vincristine and daunorubicin resistant Nalm-6 cells.

Keywords: Anticancer drugs; Drug resistance; Organotin complexes; Thioredoxin reductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxylic Acids / metabolism*
  • Cell Line, Tumor
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Maleimides / chemistry*
  • Naphthalimides / chemistry*
  • Organotin Compounds / chemistry
  • Organotin Compounds / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors*

Substances

  • Carboxylic Acids
  • Ligands
  • Maleimides
  • Naphthalimides
  • Organotin Compounds
  • Thioredoxin-Disulfide Reductase