A family of manganese complexes containing heterocyclic-based ligands with cytotoxic properties

Abstract

We describe the synthesis of three new manganese (II) complexes containing the bidentate ligands 2-(1-methyl-3-pyrazolyl)pyridine (pypz-Me) and ethyl 2-(3-(pyridine-2-yl)-1H-pyrazol-1-yl)acetate (pypz-CHCOOEt), with formula [MnX(pypz-Me)] (X = Cl1, CFSO2) and [Mn(CFSO)(pypz-CHCOOEt)] 3. Complexes 1-3 have been characterized through analytical, spectroscopic and electrochemical techniques, as well as by monocrystal X-ray diffraction analysis. The complexes show a six-coordinated Mn(II) ion though different stereoisomers have been isolated for the three compounds. Complexes 1-3, together with the previously described compounds [MnCl(pypz-H)] 4, [Mn(CFSO)(pypz-H)] 5, [Mn(NO)(pypz-H)] 6, [MnCl(HO)(pypz-H)] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and ([Mn(CFSO)((-)-L)] 8, ((-)-L = (-)-pinene[5,6]bipyridine), were tested in vitro for cytotoxic activity against NCI-H460 and OVCAR-8 cancer cell lines. The geometry of a specific compound does not seem to influence its activity in a significant extent. However, among the tested compounds those that display hydrophobic substituents on the pyrazole ring and triflate ions as labile ligands show the best antiproliferative properties. Specifically, compound 8 containing the pinene-bipyridine ligand presents an antiproliferative activity similar to that of cisplatin and higher than that of carboplatin, and displays selectivity for tumour cells. Its antiproliferative effect is due to the generation of ROS species that allow the compound to interact with DNA.

Dinuclear Iron Complexes of Iminopyridine-Based Ligands as Selective Cytotoxins for Tumor Cells and Inhibitors of Cancer Cell Migration

“…The interaction of DNA with the compounds was monitored in an agarose gel electrophoresis as previously described [18]. Briefly, we mixed 0.5 µL of supercoiled 0.5 µg/µL pUC18 DNA (Thermo Scientific, Waltham, MA, USA) with either 25, 50, 75, or 100 µM of the compounds diluted in TE buffer (10 mM Tris-HCl, pH 7.6, 1 mM EDTA) in a final volume of 20 µL.…”

“…On the other hand, the positive control, cisplatin, promotes the described effect on DNA, i.e., the migration of the CCC form decreases until it co-migrates with the OC form to reach the coalescence point [20]. We performed the same assay in the presence of H 2 O 2 , an initial activator of other ROS compounds [18]. As can be seen (Figure 1B), in the presence of H 2 O 2 all the compounds promote the appearance of a band, which is formed when both DNA strands of plasmid pUC18 are cut, named the linear form (L).…”

New Ionic Cu(II) and Co(II) DACH–Flufenamate Conjugate Complexes: Spectroscopic Characterization, Single X–Ray Studies and Cytotoxic Activity on Human Cancer Cell Lines

“…According to this report, the cytotoxic activity of a metal complex is controlled by the metal, its oxidation state, the coordinated ligands and their capacity to inhibit tumor cell growth . In this regard, extensive researches were carried out on the metal–based complexes incorporating essential metal ions such as Fe(II), Co(II), Mn(II), Cu(II) etc . Copper–an essential redox metal ion is endowed with unique properties viz ; Lewis acidity, redox activity, antitumor and apoptosis inducing capabilities.…”