4.7 Article

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

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 87, Issue -, Pages 794-800

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.09.075

Keywords

Anticancer drugs; Drug resistance; Organotin complexes; Thioredoxin reductase

Funding

  1. CAPES
  2. Deutsche Forschungsgemeinschaft (DFG) [FOR630]
  3. Dr. Kleist-Stiftung (Berlin)
  4. Koch-Stiftung (Berlin)

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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. (c) 2014 Elsevier Masson SAS. All rights reserved.

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