title: Organotin complexes containing carboxylate ligands with maleimide and naphthalimide derived partial structures: TrxR inhibition, cytotoxicity and activity in resistant cancer cells.
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.
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany.
authors.forename: Kely
authors.initials: K
authors.lastname: Navakoski de Oliveira
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Andermark
authors.affiliation: Department of Pediatric Oncology, Cologne Children's Hospital, Amsterdamer Str. 59, D-50735 Cologne, Germany.
authors.forename: Liliane A
authors.initials: LA
authors.lastname: Onambele
authors.affiliation: Department of Pediatric Oncology, Cologne Children's Hospital, Amsterdamer Str. 59, D-50735 Cologne, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Dahl
authors.affiliation: Department of Pediatric Oncology, Cologne Children's Hospital, Amsterdamer Str. 59, D-50735 Cologne, Germany. Electronic address: prokopa@kliniken-koeln.de.
authors.forename: Aram
authors.initials: A
authors.lastname: Prokop
authors.affiliation: Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106 Braunschweig, Germany. Electronic address: ingo.ott@tu-braunschweig.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
mesh_terms: D002264:Carboxylic Acids / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008301:Maleimides / Q000737:chemistry*; D053644:Naphthalimides / Q000737:chemistry*; D009947:Organotin Compounds / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors*
chemical_list: D002264:Carboxylic Acids; D008024:Ligands; D008301:Maleimides; D053644:Naphthalimides; D009947:Organotin Compounds; D013880:Thioredoxin-Disulfide Reductase
keywords: Anticancer drugs; Drug resistance; Organotin complexes; Thioredoxin reductase