Tumour Inhibiting Metal Complexes with Different Arene Moieties and Naphthoquinone Derived-Ligands

Abstract

Platinum based complexes such as cisplatin, carboplatin or oxaliplatin are widely used in cancer treatment. Nevertheless, they have shown severe side effects as well as intrinsic and acquired resistances which have led to the development of other metal based complexes such as ruthenium and osmium compounds. These compounds have demonstrated promising anticancer activity but with lower toxicity. Three of these complexes, NAMI-A, KP1019 and KP1339 have entered clinical trials with excellent results. In this work, ruthenium(II)- and osmium(II) ɳ6-arene metal complexes equipped with pharmacologically–active 1,4-naphthoquinone-derived ligands were synthesised. 1,4- Naphthoquinone derived ligands exhibit a broad range of biological effects such as anticancer, antibacterical and antimalarial activity by generating reactive oxygen species (ROS) which harm DNA and consequently induce apoptosis. These ligands can chelate to metal centres of Ru(II)- and Os(II) ɳ6-arene moieties altering the chemical and biological properties of the ligands. The arene ligand of the Ru(II) and Os(II)ɳ6-arene complexes is an important feature which stabilises the metal in the +2 oxidation state and also provides a hydrophobic face to the complex. The biological activity of Ru(II) complexes bearing different arenes having different hydrophobicity has been investigated. It is reported that the nature of the arene strongly influences the cytotoxicity, inducing extra distortion of DNA with the ability of the extended arenes to intercalate into DNA. With this aim, a series of Ru(II) and Os(II) complexes with different arene moieties and bioactive 1,4-naphthoquinone–derived ligands were synthesised and characterised by means of 1D and 2D NMR spectroscopy and elemental analysis. Several metal complexes were also characterised by single-crystal X-ray diffraction analysis. One of the complexes was used to investigate its redox behaviour with ascorbic acid which is an important biological reducing agent that protects cells in nearly all aerobic organisms.