Synthesis, characterization, anticancer and antimicrobial study of arene ruthenium(II) complexes with 1,2,4-triazole ligands containing an α-diimine moiety

Abstract

Abstract The reaction of the ruthenium arene dimers [(η 6-arene)Ru(μ-Cl)Cl]2 (where arene=benzene or p-cymene) with the ligands 4-benzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L1 ), 2-methoxybenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L2 ), 4-methylbenzylidene-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L3 ) and indole-3-carbaldehyde-3,5-di(2′-pyridyl)-4-amino-1,2,4-triazole (L4 ) in a 1:2 ratio gives the new complexes [(η 6-arene)RuCl(L)]+ [arene=C6H6 (with L=L1(1), L2(3), L4(7), with PF6 − as a counter ion, and L4 (6), with Cl− as a counter ion) or p-cymene with L=L1(2), L2(4), L3(5), L4(8) with PF6 − as a counter ion]. All complexes were fully characterized using 1H and 13C NMR, elemental analyses, UV/Vis and IR spectroscopy. The single crystal X-ray structures of ligand L2 and complex 1 have been determined. The structure of 1 has the Ru atom coordinated with the arene group and to the N,N′-bidentate ligand and to the Cl atom. The arene group occupies the apex, while the ligand and the Cl atom are at the base of a pseudo-octahedral three-legged piano stool. The cytotoxicity of these mononuclear complexes was established in the human epithelial colorectal adenocarcinoma cell line (Caco-2) and for selectivity in the non-cancerous human embryonic kidney cell line (HEK293), using 5-fluorouracil (5-FU) as the reference anticancer drug. Compounds 1 and 7 were relatively inactive toward the Caco-2 tumor cells (IC50>200), while complexes 2–5 showed moderate anti-proliferative properties (IC50>100–200). Compound 6, however, displayed better anti-proliferative properties with an IC50 value lower than that of the reference drug, 5-FU, and was therefore further investigated for its antimicrobial activity against six Gram-positive and four Gram-negative bacteria.