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-CH2COOEt), with formula [MnX2(pypz-Me)2] (X = Cl−1, CF3SO3−2) and [Mn(CF3SO3)2(pypz-CH2COOEt)2] 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 [MnCl2(pypz-H)2] 4, [Mn(CF3SO3)2(pypz-H)2] 5, [Mn(NO3)2(pypz-H)2] 6, [MnCl2(H2O)2(pypz-H)2] 7 (pypz-H = 2-(3-pyrazolyl)pyridine) and ([Mn(CF3SO3)2((−)-L)2] 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