Albumin Conjugates of Thiosemicarbazone and Imidazole-2-thione Prochelators: Iron Coordination and Antiproliferative Activity

Yu Shien Sung, Wangbin Wu, Megan A. Ewbank, Rachel D. Utterback, Michael T. Marty, Elisa Tomat

Research output: Contribution to journalArticlepeer-review

Abstract

The central role of iron in tumor progression and metastasis motivates the development of iron-binding approaches in cancer chemotherapy. Disulfide-based prochelators are reductively activated upon cellular uptake to liberate thiol chelators responsible for iron sequestration. Herein, a trimethyl thiosemicarbazone moiety and the imidazole-2-thione heterocycle are incorporated in this prochelator design. Iron binding of the corresponding tridentate chelators leads to the stabilization of a low-spin ferric center in 2 : 1 ligand-to-metal complexes. Native mass spectrometry experiments show that the prochelators form stable disulfide conjugates with bovine serum albumin, thus affording novel bioconjugate prochelator systems. Antiproliferative activities at sub-micromolar levels are recorded in a panel of breast, ovarian and colorectal cancer cells, along with significantly lower activity in normal fibroblasts.

Original languageEnglish (US)
Pages (from-to)2764-2768
Number of pages5
JournalChemMedChem
Volume16
Issue number18
DOIs
StatePublished - Sep 16 2021

Keywords

  • albumin
  • cancer
  • imidazole-2-thione
  • iron chelation
  • thiosemicarbazone

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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