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

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 Schwannlike cells, thus significantly reducing their tumorigenic potential. Additionally, FETPY substantially suppressed tumor growth in lowand 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.

1,3,5-Triaza-7-phosphaadamantane and Cyclohexyl Groups Impart to Di-Iron(I) Complex Aqueous Solubility and Stability, and Prominent Anticancer Activity in Cellular and Animal Models

“…The bis-cyclopentadienyl core {Fe 2 Cp 2 (CO) x } (Cp = η 5 -C 5 H 5 , x = 2–3) offers substantial ligand diversity and synthetic opportunities, originating from the cooperative effects typical of a dimetallic system. − Recently, we unveiled the anticancer potential of diiron­(I) complexes obtained from the commercially available, inexpensive, and easy-to-handle [Fe 2 Cp 2 (CO) 4 ]. − Specifically, aminocarbyne species (Figure B, structure III ) are obtained through a straightforward two-step synthetic route, that is multigram scalable and does not require the isolation of intermediates. − …”