Anionic dinitrosyl iron complexes – new nitric oxide donors with selective toxicity to human glioblastoma cells

Abstract

Low-molecular-weight dinitrosyl iron complexes (DNICs) with functional sulfur-containing ligands are structurally related to nitrosylated ferredoxines. DNICs are nitric oxide (NO) donors, and they may be promising therapeutic agents because of versatile biological roles of NO. Two new anionic dinitrosyl iron complexes with S-donor ligands, (CH3)4N[Fe1(SC6H4NO2)2(NO)2]⋅СH2Cl2 (I) and (CH3)4N[Fe1(SC5H3N2O2)2(NO)2] (II), have been synthesized by direct interaction of alkali solutions of the reduced Na2[Fе2(S2O3)2(NO)4]⋅4H2O and nitro derivatives of thiophenol and thiopyridine. The structure and properties of new DNICs in solid were studied with X-ray analysis, IR, Mossbauer, EPR spectroscopy, and SQUID magnetometry. To evaluate antitumor potential of these NO donors, their cytotoxicity was studied on several cancer cell lines (A-172, M-HeLa, and HepG2) and non-cancerous Vero cells. Human glioma A-172 cells were found to be highly sensitive to complexes I and II relative to other cell lines. It is assumed that high sensitivity of A-172 cells to I and II is related to the formation of nitrosyl intermediates providing prolonged NO release rather than NO donor properties of the complexes.