title: 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, (1)H and (13)C 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.
authors: Faculty of Veterinary Medicine, University of Belgrade, Bulevar oslobodjenja 18, 11000 Belgrade, Serbia.
authors: Milena
authors: M
authors: Krstić
authors: Sofija P
authors: SP
authors: Sovilj
authors: Sanja
authors: S
authors: Grgurić-Šipka
authors: Ivana Radosavljević
authors: IR
authors: Evans
authors: Sunčica
authors: S
authors: Borozan
authors: Juan Francisco
authors: JF
authors: Santibanez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D000081007:Cymenes; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry*; D010640:Phenothiazines / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000970:Antineoplastic Agents; D000081007:Cymenes; D016166:Free Radical Scavengers; D039821:Monoterpenes; D010640:Phenothiazines; D017975:Ruthenium Compounds; C007210:4-cymene