Novel 8-Hydroxyquinoline-Derived V(IV)O, Ni(II), and Fe(III) Complexes: Synthesis, Characterization, and In Vitro Cytotoxicity Against Tumor Cells

Abstract

We report the synthesis and characterization of five novel metal complexes. Three of them are vanadium complexes with the general formula [VO(Ln)2], where Ln are Schiff bases derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with either 4-(2-aminoethyl)morpholine (L1), 3-morpholinopropylamine (L2) or 1-(2-aminoethyl)piperidine (L3). The two other metal complexes are [Ni(L1)2] and [Fe(L1)2]Cl. They were characterized by analytical, spectroscopic (Fourier transform infrared, UV-visible absorption), and mass spectrometric techniques as well as by single-crystal X-ray diffraction (for all [VO(Ln)2] complexes and [Ni(L1)2]). While, in the crystal structure, the V(IV)O complexes show distorted square-pyramidal geometry with the ligands bound as bidentate through quinolate NO donors, the Ni(II) complex shows octahedral geometry with two ligand molecules coordinated through NNO donors. Stability studies in aqueous media revealed that the vanadium complexes are not stable, undergoing oxidation to VO2(L), which was corroborated by 51V NMR and MS. This behavior is also observed in organic media, though at a significantly slower rate. The Ni complex exhibited small spectral changes over time in aqueous media. Nonetheless, all compounds show enhanced stability in the presence of bovine serum albumin (BSA). Fluorescence studies carried out for the Ni(II) and Fe(III) complexes indicate reversible binding to albumin. The cytotoxicity of the L1 metal complexes was assessed on melanoma (B16F10 and A375) and colon cancer (CT-26 and HCT-116) cell lines, with 5-fluorouracil (5-FU) as a reference drug. The V- and Ni complexes showed the lowest IC50 values (<10 μM) in either A375 or HCT-116 cells after 48 h of incubation, while the Fe(III) complex presented minimal antiproliferative effects. The complexes were generally more cytotoxic to human than murine cancer cells. Synergistic in vitro studies with 5-FU revealed antagonism in most cases, except in A375 cells, where an additive effect was observed for the combination with the V-complex. Overall, these compounds show promising potential for cancer treatment, mostly for melanoma