Synthesis, structural and spectroscopic characterization, in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido( p-cymene) complexes of ruthenium(II) containing N-alkylphenothiazines

Abstract

Three new ruthenium(II) complexes 1– 3 containing N-alkylphenothiazine molecules were synthesized by reaction of [RuCl 2(η 6- p-cymene)] 2 with chlorpromazine hydrochloride ( 1), trifluoperazine dihydrochloride ( 2) or thioridazine hydrochloride ( 3). The compounds of the general formula L[RuCl 3(η 6- p-cymene)] were characterized by elemental analysis and spectroscopic methods (FT-IR, UV–Vis, 1H and 13C NMR). Complex 2 was structurally characterized by single crystal X-ray diffraction. In vitro cytotoxic activity of complexes 1– 3 were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon carcinoma) and IM9 (myeloma multiple cells). The highest cytotoxicity (12.1 ≤ IC 50 ≤ 17.3 μM) and induced a total (SW-480) or almost total cell death (MCF-7, MDA-MB-453) at 25 μM in 48 h of treatment were observed for complex 2. The influence of three different doses (0.4, 4.5 and 90.4 μM/kg bw) of complex 2 on activities of antioxidants enzymes (superoxide dismutase (SOD) and catalase (CAT)) and lactate dehydrogenase (LDH) were investigated under physiological conditions. The effects on nitrite production ( NO 2 − ) and level of erythrocytes malondialdehyde (MDA) in rats blood were evaluated, too.