A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(μ-CO){μ-η1:η3C(R′)C(R″)CN(R)(Y)}]CF3SO3 (2–7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69–95% yields from the reactions of diiron μ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR,1H and13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R′ = R″ = Me) and 3a (R = CH2CH=CH2, Y = R′ = Me, R″ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV–Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol–water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2–7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R′ = R″ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).

Braccini S., Rizzi G., Biancalana L., Pratesi A., Zacchini S., Pampaloni G., et al. (2021). Anticancer diiron vinyliminium complexes: A structure– activity relationship study. PHARMACEUTICS, 13(8), 1-25 [10.3390/pharmaceutics13081158].

Anticancer diiron vinyliminium complexes: A structure– activity relationship study

Zacchini S.;
2021

Abstract

A series of 16 novel diiron complexes of general formula [Fe2Cp2(CO)(μ-CO){μ-η1:η3C(R′)C(R″)CN(R)(Y)}]CF3SO3 (2–7), bearing different substituents on the bridging vinyliminium ligand, was synthesized in 69–95% yields from the reactions of diiron μ-aminocarbyne precursors with various alkynes. The products were characterized by elemental analysis, IR,1H and13C NMR spectroscopy; moreover the X-ray structures of 2c (R = Y = CH2Ph, R′ = R″ = Me) and 3a (R = CH2CH=CH2, Y = R′ = Me, R″ = H) were ascertained by single-crystal X-ray diffraction studies. NMR and UV–Vis methods were used to assess the D2O solubility, the stability in aqueous solution at 37 °C and the octanol–water partition coefficients of the complexes. A screening study evidenced a potent cytotoxicity of 2–7 against the A2780 cancer cell line, with a remarkable selectivity compared to the nontumoral Balb/3T3 cell line; complex 4c (R = Cy, Y = R′ = R″ = Me) revealed as the most performant of the series. The antiproliferative activity of a selection of complexes was also assessed on the cisplatin-resistant A2780cisR cancer cell line, and these complexes were capable of inducing a significant ROS production. Moreover, ESI-MS experiments indicated the absence of interaction of selected complexes with cytochrome c and the potentiality to inhibit the thioredoxin reductase enzyme (TrxR).
2021
Braccini S., Rizzi G., Biancalana L., Pratesi A., Zacchini S., Pampaloni G., et al. (2021). Anticancer diiron vinyliminium complexes: A structure– activity relationship study. PHARMACEUTICS, 13(8), 1-25 [10.3390/pharmaceutics13081158].
Braccini S.; Rizzi G.; Biancalana L.; Pratesi A.; Zacchini S.; Pampaloni G.; Chiellini F.; Marchetti F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/830139
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