New ruthenium(II) complexes with N-alkylphenothiazines: synthesis, structure, in vivo activity as free radical scavengers and in vitro cytotoxicity.
Three new complexes of the general formula L[RuCl(3)(DMSO)(3)] (1-3), where L = chlorpromazine hydrochloride, trifluoroperazine dihydrochloride or thioridazine hydrochloride, were prepared and characterized by elemental analysis and spectroscopic methods (FT-IR, UV-Vis, (1)H NMR and (13)C NMR). In addition, the crystal structure of the complex 2 containing trifluoroperazine dihydrochloride was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P2(1)/n, with a = 10.4935(7) A, b = 18.6836(12) A, c = 19.9250(13) A, beta = 98.448(2) degrees, V = 3864.0(4) A(3). The structure was refined to the agreement factors of R = 4.79%, R(w) = 11.23%. The effect of three different doses (0.4, 4.5 and 90.4 microM/kg bw) of complex 2 on superoxide dismutase (SOD) and catalase (CAT) activity was investigated under physiological conditions. Influence on nitrite production (NO(2)(-)) and the level of erythrocytes malondialdehyde (MDA) in rats blood was also evaluated. Complex 2 did not affect the CAT enzyme activity in vivo and did not cause the hydroxyl radicals production. In the 0.4 and 4.5 microM/kg bw doses it showed almost the same or lower SOD activity and nitrite levels, while the dose of 90.4 microM/kg bw significantly increased these parameters. Finally, the cytotoxicity of complexes were assayed in four human carcinoma cell lines MCF-7, MDA-MB-453 (breast carcinoma), SW-480 (colon adenocarcinoma) and IM9 (myeloma multiple cells). Antiproliferative activity in vitro with low IC(50) during 48 h of treatment was observed.
Krstić
Milena
M
Faculty of Veterinary Medicine, University of Belgrade, Bulevar oslobodjenja 18, 11000 Belgrade, Serbia.
Sovilj
Sofija P
SP
Grgurić-Sipka
Sanja
S
Radosavljević Evans
Ivana
I
Borozan
Suncica
S
Santibanez
Juan Francisco
JF
Kocić
Jelena
J
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010640:Phenothiazines / Q000737:chemistry*; D051381:Rats; D012428:Ruthenium / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000378:metabolism
D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D005609:Free Radicals; D009942:Organometallic Compounds; D010640:Phenothiazines; D012428:Ruthenium; D002374:Catalase; D013482:Superoxide Dismutase; C031637:phenothiazine