Synthesis, Characterization and Cytotoxicity Evaluation on Monocytic Cell Line THP1 of Ru(II) Complexes with 1, 2-Disubstituted Benzimidazoles

Abstract

INTRODUCTION: The medicinal value of cis-Platin has led to the discovery of alternative metal complexes with better medicinal properties. 1 Ruthenium based metal complexes have novel anticancer properties. 2 Ruthenium complexes with ligands containing groups as amines, imines and imidazoles such as [ImH][trans-Ru(III)Cl 4 (dmso-S)(Im)](NAMI-A; Im = Imidazole, dmso = dimethylsulfoxide) and [IndH][trans-Ru(III) Cl 4 (Ind) 2 ] (KP1019; Ind = indazole), have successfully completed phase-1clinical trials and are scheduled to enter phase 2 trials in the near future. 14,3,4 In addition, benzimidazole derivatives show significant antiinflammatory, antioxidant, gastroprotective and antiparasitic activities. Therefore, large number of its metal complexes has been synthesized and applied in urea recognition, DNA binding, catalysis and chemical sensors in biological systems. 5,6 With bisbenzimidazole derivatives, ruthenium compounds exhibit powerful cytotoxicity against ovarian carcinoma cells, which creates the underlying mechanism of anticancer functions. 7,8 Ruthenium is an alternative to platinum, because of accessible oxidation states and less toxic than platinum counterpart, which makes them significant for anticancer activities under physiological conditions. 9,10 This is due to the ability of ruthenium to mimic iron in the binding to biological molecules, such as albumin and transferrin, although platinum drugs can also bind to the proteins. 11 Since rapidly dividing cells, such as cancerous cells, more demand for iron, transferrin receptors are overexpressed, so that ruthenium-based medicines can be delivered more effectively to cancerous cells. 12 Furthermore, activation by "reduction" mechanisms may be responsible for toxicity of some ruthenium compounds. 13 In the last two decades, a new approach to the treatment of cancer, known as Targeted Medicine and Targeting Cellular Signaling Path of Cancer Cells, starts producing highly effective cancer treatment with very little serious side effects. 15, 16 Some of them, e.g. Imatinib mesylate and Erlotinib hydrochloride have