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U cilju pronalaženja adekvatne terapije u lecenju maligniteta kompleksi rutenijuma pokazali su zavidan potencijal. Kompleksi Ru(II) sa N-alkilfenotiazinima, hlorpromazinom, trifluoperazinom i tioridazinom, korišceni su u ispitivanju mogucih puteva apoptoze u K562 celijama. Ispitivana je spektrofotometrijski ekstracelularna LDH, ekspresija COX-2, t-JNK, p-JNK i b-aktina imunohemijski nakon SDS elektroforeze. Kompleks Ru(II) sa trifluoperazinom u koncentraciji od 10 μM smanjuje ekspresiju t-JNK, inhibira COX-2 oko 42%, znacajno povecava kolicinu ekstracelularne LDH u odnosu na netretirane K562 celije i time potvrdjuje apoptozu ovih celija Ruthenium complexes are of significant interest in the treatment of malignancies. Ru(II) complexes with N-alkylphenothiazines (chlorpromazine, trifluoperazine, and thioridazine) were used in the study of possible apoptosis pathways in K562 cells. Spectrophotometrically extracellular LDH was quantified and immunochemical expression of COX-2, t-JNK, p-JNK and b-actin after SDS electrophoresis was determined. The Ru(II) complex with trifluoperazine at a concentration of 10 μM reduced t-JNK expression, inhibited COX-2 by about 42%, significantly increased the amount of extracellular LDH compared to the untreated K562 cells and thus confirmed apoptosis. Kratki izvodi radova

Rhenium complexes merit particular attention in the area of metallodrug design due to rhenium’s broad spectrum of oxidation states and consequently, the possibility to design compounds of a great structural diversity. Thus, the synthesis, chemical characterization and antitumor activity in vitro of the three Re(V) complexes is described. Novel compounds were obtained via reaction of [ReOCl3(PPh3)2] with corresponding ligands (pyridine-2-carboxylic acid, 3-methylpyridine-2-carboxylic acid and 6-methylpyridine- 2-carboxylic acid) in acetonitrile at 78 °C for 3h. The complexes were fully characterized using NMR, IR, MS and elemental analysis. Their octahedral geometry with bidentate N^O ligand was confirmed by X-ray diffraction analysis. Antiproliferative effect was determined by MTT assay and only the complex with pyridine-2-carboxylic acid (1) showed dose-dependent cytotoxic potential, particularly toward triple-negative breast adenocarcinoma cells MDA-MB-231 with IC50 68.90 ± 1.73 μM and pancreatic adenocarcinoma cells PANC-1 with IC50 69.8 ± 2.3 μM. Drug combination studies in PANC-1 cells with 1 and Verapamil hydrochloride (VRP) showed slight arrest of cell cycle in the S phase and also it increase its antiproliferative potential to IC50 51.4 ± 2.8 μM. Part of the research included a depletion of the glutathione (GSH) level by L-buthionine-sulfoximine (L-BSO) at sub-toxic concentrations (100 μM) in PANC-1 cells which caused an increase of activity of 1 to the IC50 57.67 ± 6.51 μM. Book of Abstracts

Ruthenium complexes are of significant interest in the treatment of malignancies. Ru(II) complexes with N-alkylphenothiazines (chlorpromazine, trifluoperazine, and thioridazine) were used in the study of possible apoptosis pathways in K562 cells. Spectrophotometrically extracellular LDH was quantified and immunochemical expression of COX-2, t-JNK, p-JNK and -actin after SDS electrophoresis was determined. The Ru(II) complex with trifluoperazine at a concentration of 10 μM reduced t-JNK expression, inhibited COX-2 by about 42%, significantly increased the amount of extracellular LDH compared to the untreated K562 cells and thus confirmed apoptosis. U cilju pronalaženja adekvatne terapije u lečenju maligniteta kompleksi rutenijuma pokazali su zavidan potencijal. Kompleksi Ru(II) sa N-alkilfenotiazinima, hlorpromazinom, trifluoperazinom i tioridazinom, korišćeni su u ispitivanju mogućih puteva apoptoze u K562 ćelijama. Ispitivana je spektrofotometrijski ekstracelularna LDH, ekspresija COX-2, t-JNK, p-JNK i β-aktina imunohemijski nakon SDS elektroforeze. Kompleks Ru(II) sa trifluoperazinom u koncentraciji od 10 µM smanjuje ekspresiju t-JNK, inhibira COX-2 oko 42%, značajno povećava količinu ekstracelularne LDH u odnosu na netretirane K562 ćelije i time potvrdjuje apoptozu ovih ćelija.