FETPY: a Diiron(I) Thio-Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo

  • J Med Chem. 2024 May 9;67(9):7553-7568. doi: 10.1021/acs.jmedchem.4c00377.
Ekatarina Mihajlović  1 ,  Lorenzo Biancalana  2 ,  Sanja Jelača  1 ,  Lorenzo Chiaverini  2 ,  Biljana Dojčinović  3 ,  Duško Dunđerović  4 ,  Stefano Zacchini  5 ,  Sanja Mijatović  1 ,  Danijela Maksimović-Ivanić  1 ,  Fabio Marchetti  2
Affiliations
  • 1. Department of Immunology, Institute for Biological Research "Siniša Stanković" - National Institute of the Republic of Serbia, University of Belgrade, Belgrade 11108, Serbia.
  • 2. Department of Chemistry and Industrial Chemistry, University of Pisa, Via Giuseppe Moruzzi 13, Pisa I-56124, Italy.
  • 3. Institute of Chemistry, Technology and Metallurgy University of Belgrade, Njegoševa 12, Belgrade 11000, Serbia.
  • 4. Institute of Pathology, School of Medicine University of Belgrade, dr Subotića 1, Belgrade 11000, Serbia.
  • 5. Department of Industrial Chemistry "Toso Montanari", University of Bologna, Via P. Gobetti 85, Bologna I-40129, Italy.
PMID: 38639401 DOI: 10.1021/acs.jmedchem.4c00377
Abstract

FETPY, an organo-diiron(I) complex, showed strong cytotoxicity across a panel of human and mouse Cancer cell lines, combined with an outstanding selectivity compared to nonmalignant cells. Enhanced iron uptake in aggressive, low-differentiated cell lines, caused membrane lipid peroxidation, which resulted in Ferroptosis in human ovarian Cancer cells. FETPY induced significant morphological changes in murine B16-F1 and B16-F10 melanoma cells, leading to senescence and/or trans-differentiation into Schwann-like cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in low- and high-grade syngeneic melanoma models when administered in a therapeutic regimen. FETPY is featured by satisfactory water solubility (millimolar range), an amphiphilic character (Log Pow = -0.17), and excellent stability in a biological medium (DMEM). These important requisites for drug development are rarely met in iron complexes investigated so far as possible Anticancer agents. Overall, FETPY holds promise as a safe and potent targeted antitumor agent.

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