Evaluation of trimetallic Ru(II)- and Os(II)-Arene complexes as potential anticancer agents

Schiff-base ligands, tris-2-(salicylaldimine ethyl)amine and tris 2 (2 pyridylimine ethyl)amine (1 and 2) were prepared and complexed to Ru(II) and Os(11) entities to form new trimetallic complexes (3-10). The complexes are air- and moisture-stable and have been characterized fully using elemental analysis, FT-IR and NMR spectroscopy as well as HR-ESI-TOF-MS spectrometry. Related mononuclear analogues (11-14) were also prepared via the Schiff-base condensation reaction of propyl amine and the appropriate aldehyde to form propysalicylaldimine and propyl-2-pyridylimine ligands. Upon complexation with the respective metal dimers, ([OsCl2(p-cym)](2) and [OsBr2(p-cym)](2)) complexes (11-14) formed and were characterized by elemental analysis, NMR, FT-IR spectroscopy and mass spectrometry. The cytotoxicity of the trimetallic complexes (3-10) and their mononuclear analogues were established against human osteosarcoma (MG63), human ovarian (A2780cisR; cisplatin-resistant) cancer cells and model human non-cancerous cells (KMST6, fibroblast). All the complexes exhibited moderate to high anti-cancer activities and the most potent complexes were further evaluated for their ability to inhibit DNA topoisomerase I (Topo I) an enzyme key to cellular genetic processes, such as DNA replication and transcription. (C) 2014 Elsevier B.V. All rights reserved.