Towards anticancer metal complexes based on hydroxyquinoline-derived ligands

Abstract

Cancer is one of the main causes of death worldwide. According to the World Health Organization (WHO), the number of diagnosed cancer patients is expected to rise by about 70% over the next two decades. Ever since the serendipitous discovery of cisplatin, and as the role of metals in anticancer drugs are studied more in depth, a variety of metal-based anticancer drugs has been synthesized and studied. Out of all the metals, ruthenium-based drugs have been found to exhibit promising anticancer activity. NAMI-A and KP1019 are key examples of ruthenium-based anticancer drugs. A new class of ruthenium derivatives, the "piano-stool" [(η6-arene)Ru(X)(Y)(Z)] complexes, have gained attention as anticancer agents. The arene stabilises RuII and the ligands X, Y, and Z can serves to form either mono, bi, or tridentate ligand to provide better anticancer activity. The quinoline scaffold is found in a large number of natural and commercial products, and its derivatives are constantly being researched. From quinoline derivatives, 8-hydroxyquinoline and its derivatives are widely used as drugs and it exhibits a compelling coordinating ability and good recognition properties to form complexes with divalent metal ions through chelation. Hence it is widely used for analytical and separation purposes as well as for metal chelation. Since an imbalance of metal ions causes numerous health issues, 8-hydroxyquinoline can successfully serve as a potent chelator to restore metal balance to treat metal-related diseases. For this project, 8-hydroxyquinoline and its derivative were synthesised by functionalising the hydroxyl group of 8-hydroxyquinoline with suberic acid which were then complex with the various [MCl2(η6-p-cymene/η5-Cp*)] dimers. These complexes were characterised with 1D and 2D NMR spectroscopy, mass spectrometry and elemental analysis to confirm the structures. Stability studies in DMSO and D2O solvent were also carried out for selected complexes to observe the behaviour during cell viability test. In vitro studies was conducted for selected complexes. Complexes 3a and 3c showed higher in anticancer activity than other complexes. Across the cell lines, all complexes displayed lower in anticancer activity on SiHa cell line.