Antitumor activity and DNA binding studies on rare earth metal complexes with all-trans retinoic acid and l-glutamic acid

Abstract

Four new complexes have been synthesized by the reaction of rare earth (III) nitrate with all-trans retinoic acid as the first ligand and L-glutamic acid as the second ligand in an alcoholic solution (pH = 6.5–7.0) with the aim to develop new antitumor drugs. The composition of the complexes has been characterized by elemental analysis, molar conductivity, IR spectroscopy, ¹H NMR spectroscopy, thermogravimetric analysis and UV-vis methods. The general molecular formula of the complexes was determined to be REL₂L′ (RE = Nd, Eu, La, Sc, L = all-trans retinoic acid, L′ = L-glutamic acid). The antitumor activities of complexes and corresponding ligands were tested by MTT methods. The results indicate that the four rare earth complexes possess different degrees of inhibiting effects on HepG2, A549 and HeLa cells. The suppression ratio of the complexes against the tested tumour cells is superior for the two ligands and RE(III) ions. Especially, the EuL₂L′ showed the most obvious antitumor activity on HepG2 and HeLa cells. To investigate the mechanism of inhibition of the complexes, EuL₂L′ reacting with DNA was studied by fluorescence spectra, viscosity, UV and CD spectra, and the results showed that the mode of interaction was mainly by intercalation, which may be the one of the important reasons for the highest antitumor activity of the EuL₂L′ complex. The results obtained in this study provide certain ideas and an experimental basis for the development of highly efficient and rare earth antitumor drugs that have low toxicity.