FETPY: a Diiron(I) Thio–Carbyne Complex with Prominent Anticancer Activity In Vitro and In Vivo
Ekatarina Mihajlović, Lorenzo Biancalana, Sanja Jelača, Lorenzo Chiaverini, Biljana Dojčinović, Duško Đunđerović, Stefano Zacchini, Sanja Mijatović, Danijela Maksimović‐Ivanić, Fabio Marchetti
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 P ow = −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.