Iodide analogs of arsenoplatins—potential drug candidates for triple negative breast cancers

Ðenana Miodragović, Wenan Qiang, Zohra Sattar Waxali, Željko Vitnik, Vesna Vitnik, Yi Yang, Annie Farrell, Matthew Martin, Justin Ren, Thomas V. O’halloran

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Patients with triple negative breast cancers (TNBCs)—highly aggressive tumors that do not express estrogen, progesterone, and human epidermal growth factor 2 receptors—have limited treatment options. Fewer than 30% of women with metastatic TNBC survive five years after their diagnosis, with a mortality rate within three months after a recurrence of 75%. Although TNBCs show a higher response to platinum therapy compared to other breast cancers, drug resistance remains a major obstacle; thus, platinum drugs with novel mechanisms are urgently needed. Arsenoplatins (APs) represent a novel class of anticancer agents designed to contain the pharmacophores of the two FDA approved drugs cisplatin and arsenic trioxide (As2O3) as one molecular entity. Here, we present the syntheses, crystal structures, DFT calculations, and antiproliferative activity of iodide analogs of AP-1 and AP-2, i.e., AP-5 and AP-4, respectively. Antiproliferative studies in TNBC cell lines reveal that all AP family members are more potent than cisplatin and As2O3 alone. DFT calculations demonstrate there is a low energy barrier for hydrolysis of the platinum-halide bonds in arsenoplatins, possibly contributing to their higher cytotoxicities compared to cisplatin.

Original languageEnglish (US)
Article number5421
JournalMolecules
Volume26
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • Antiproliferative activity
  • Arsenic trioxide
  • Arsenoplatin
  • Cisplatin
  • DFT
  • Triple negative breast cancers
  • X-ray structure

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Iodide analogs of arsenoplatins—potential drug candidates for triple negative breast cancers'. Together they form a unique fingerprint.

Cite this