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Zagreb, Croatia

Orsolic N.,University of Zagreb | Car N.,PLIVA Inc
Tumor Biology | Year: 2014

Nephrotoxicity, hepatotoxicity, myelosuppression, and genotoxicity are the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Hyperthermia enhances the clastogenicity of cisplatin. In addition, hyperthermia is a promising approach for cancer therapy because it not only kills cancer cells directly, but also activates anti-cancer immunity as an indirect effect. The aim of this study was to determine whether preventive treatment with quercetin (QU) can reduce cisplatin-induced DNA damage in liver, kidney and blood cells and whether QU has the potential to serve as a beneficial supplement before cisplatin hyperthermal intraperitoneal chemotherapy (HIPEC) in order to gain immunomodulatory responses of mice to the tumor. Preventive treatment of mice with QU (50 mg kg-1) had a protective effect on cisplatin-induced DNA damage in normal cells, except kidney cells, in both normothermic and hyperthermic conditions without interfering with the antitumor efficacy of the combined regimen. Immunostimulation by QU is stressed as an important factor in the tumor-inhibiting effect of hyperthermia in addition to the well known selective heat killing of neoplastic cells. In conclusion, these results suggested that preventive treatment with QU could protect the blood, liver and kidney cells of mice against HIPEC-induced injury and increase survival of mice by improving the antitumor adaptive immunity with hyperthermia. © 2014 International Society of Oncology and BioMarkers (ISOBM). Source

Racane L.,University of Zagreb | Mihalic Z.,University of Zagreb | Ceric H.,PLIVA Inc | Popovic J.,Ruder Boskovic Institute | Tralic-Kulenovic V.,University of Zagreb
Dyes and Pigments | Year: 2013

The efficient synthesis, 1H and 13C NMR characterization, crystal and molecular structure, DFT calculations of 6-[(2-hydroxy-1-naphthyl)diazenyl]-2-methylbenzothiazole, as well as DFT calculations of 6-[(2-hydroxy-1-naphthyl)diazenyl]benzothiazole, are reported. Single-crystal X-ray diffraction data show that crystals of the azo dye derived from 2-methylbenzothiazole is principally composed of the hydrazone form. 2D NMR techniques (COSY, HMQC and HMBC) were used to assign 1H and 13C chemical shifts for each azo dye in DMSO and CHCl3 solution. Azo-hydrazone tautomerism of the dyes was investigated jointly by 13C NMR and DFT calculations. All three approaches show that in solution the equilibrium is only slightly shifted towards the hydrazone form. The very good agreement between the three differently obtained equilibrium constants suggest M06-2X/6-311+G(d,p)-SMD as the level of theory of choice for quantum-mechanical calculations of these and similar compounds in solution. © 2012 Elsevier Ltd. All rights reserved. Source

Milovac N.,University of Zagreb | Juretic D.,University of Zagreb | Kusic H.,University of Zagreb | Dermadi J.,PLIVA Inc | Bozic A.L.,University of Zagreb
Industrial and Engineering Chemistry Research | Year: 2014

The UV/H2O2 process was applied for the degradation of aromatic carboxylic acids (ACAs). Benzoic acid, salicylic acid, gentisic acid, and gallic acid are chosen as typical water pollutants representing ACAs with the increased number of hydroxyl groups. The effect of the structural characteristics of ACAs and UV/H2O2 process parameters on their degradation kinetics was investigated by a statistical/empirical approach employing the design of experiments and response surface methodology. Different optimal conditions for maximal degradation rates were established, while degradation rates followed the decreasing order benzoic acid > salicylic acid > gentisic acid > gallic acid with the increasing number of hydroxyl groups. The inversed order was established in the case of mineralization kinetics. Structurally influenced degradation pathways of studied ACAs, with the shared sequence related to the preferable hydroxylation position at the benzene ring, are reflected in the observed changes in the biodegradability and toxicity toward Vibrio fischeri during UV/H2O2 treatment. © 2014 American Chemical Society. Source

Kwokal A.,PLIVA Inc | Roberts K.J.,University of Leeds
CrystEngComm | Year: 2014

The ability to direct the surface crystallisation of different polymorphs of entacapone by tuning the electrochemical potential of Au(100) templates is demonstrated. Under quiescent conditions, without polarization (at open circuit potential), entacapone crystallises in its stable form A on the template surface and concomitantly in its metastable form D in the bulk solution. When Au(100) is negatively polarized (-150 mV), form D is still formed in the bulk solution but the metastable form α is found to crystallise at the edges of the template. Both crystals of form A and α were observed to grow epitaxially over the Au template surface. The electrochemical templating effect is consistent with the polarisation changing the structure of the initially adsorbed layers of supersaturated solution at the template surface which directs the nuclei formation and the subsequent crystal growth processes. This study demonstrates, for the first time, the direction of polymorphic form using a low field polarized nucleation template. © 2014 the Partner Organisations. Source

Leksic E.,PLIVA Inc | Pavlovic G.,University of Zagreb | Mestrovic E.,PLIVA Inc
Crystal Growth and Design | Year: 2012

Four novel lamotrigine cocrystals, namely, 1:1 lamotrigine:phthalimide (1), 1:1:1 lamotrigine:pyromellitic diimide:DMF (2), 2:1:0.64 lamotrigine:caffeine: 3-pentanone (3), and 1:1 lamotrigine:isophthaldehyde (4), were discovered using a combined hot-stage thermomicroscopy and differential-scanning calorimetry screening technique. The utilized cocrystal screening method is rapid, requires the use of small amounts of material, and is highly suitable for compounds that are prone to solvate formation. The structurally characterized cocrystals were prepared in an attempt to develop lamotrigine cocrystals based on cocrystal formers involving carbonyl and amide functional groups. The prepared cocrystals are sustained by N-H(amide)•••N(pyridyl), N-H(amino) •••O(amide), and N-H(amino)•••O(carbonyl) hydrogen bonds. © 2012 American Chemical Society. Source

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