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Anticancer Metal Complexes: Synthesis and Cytotoxicity Evaluation by the MTT Assay
Published on: November 10, 2013
Diiron(I) Complexes with Promising Anticancer Properties Obtained by CO-To-Isocyanide Substitution of [Fe2Cp2(CO)4]
Sara Benetti1, Giulia Salluce2, Axia Marlin2
1University of Pisa , Department of Chemistry and Industrial Chemistry, Via Moruzzi 13, 56124Pisa, Italy.
Abstract:
The diiron(I) complexes [Fe2Cp2(CNR)3{CN(Me) (R)}][CF3SO3] ([2a-b][CF3SO3], R = Xyl, Cy; Xyl = 2,6-C6H3Me2, Cy = cyclohexyl) and [Fe2Cp2(CNR)2{CN(Me) (R)}2][CF3SO3]2 ([3a-c][CF3SO3]2, R = Xyl, Cy, Me) were synthesized in moderate-to-high yields from [Fe2Cp2(CO)4]. They were characterized by IR and NMR spectroscopy and single-crystal X-ray diffraction in five representative cases. The electrochemical behavior of [2a][CF3SO3] and [3a][CF3SO3]2 was investigated by cyclic voltammetry and IR-spectroelectrochemistry, assisted by DFT calculations. UV-vis and 1H NMR studies showed ≥84% of each complex remaining intact after 72 h of incubation at 37 °C in aqueous media. Complexes [3a-c][CF3SO3]2 displayed significant aqueous solubility, and [2b][CF3SO3] and [3a-b][CF3SO3]2 exhibited amphiphilic character (-1 < Log Pow < +1). The monocationic species [2a-b][CF3SO3] exerted strong cytotoxicity in A2780, A549, and U87 cancer cell lines, with [2a][CF3SO3] showing IC50 values in the nanomolar range. Among dicationic complexes, [3a][CF3SO3]2 exhibited significant activity despite limited cellular uptake, whereas [3b-c][CF3SO3]2 were inactive. Compounds [2a][CF3SO3], [2b][CF3SO3] and [3a][CF3SO3]2 impaired mitochondrial bioenergetics without detectable elevation of intracellular ROS levels in both A549 and U87 cells. No significant interaction with double-stranded DNA was detected by ethidium bromide displacement assays. Conversely, fluorescence titrations with bovine serum albumin indicated the formation of 1:1 adducts for [2a]+ and [3a]2+.
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