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

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.