The cytotoxic effect of Ru(II) complexes with 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridyl)-1H-pyrazole-4-carboxylic acid methyl ester: Synthesis, X-ray structure and DNA damage potential

摘要

A series of arene ruthenium(II) complexes, 1a-3a, with the general formula [(eta(6)-arene)Ru(L)Cl-2] (where arene = p-cymene, hexamethylbenzene and benzene, respectively, and L = 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridyl)-1H-pyrazole-4-carboxylic acid methyl ester) were synthesized and characterized by elemental analysis, MS, IR and H-1 NMR spectroscopy. The stability of selected complexes was assessed by UV-Vis spectroscopy over 24 and 48 hour periods. The synthesized complexes were evaluated for in vitro experiments using HL-60, NALM-6, WM-115 and COLO-205, and they showed low cytotoxic activity. The most active compound, 2a, possesses IC50 = 41.17 +/- 3.68 mu M, which is comparable to the reference compound quercetin. X-ray crystallographic analysis of compound 1a found that the ruthenium complex adopts a piano-stool type of geometry, with crystal packing stabilized by a 3-D net of O-H center dot center dot center dot Cl and C-H center dot center dot center dot Cl type hydrogen bonds, the latter forming dimers in the crystal lattice. The most active complexes in the cytotoxicity experiments were selected for evaluation of the damage percentage in NALM-6 cells by a comet assay: the extent of DNA fragmentation in the lymphoblastic leukemia cells indicated that the analyzed ruthenium(II) complexes triggered DNA damage. (C) 2019 Elsevier Ltd. All rights reserved.