BELUPO Pharmaceuticals Inc.

Koprivnica, Croatia

BELUPO Pharmaceuticals Inc.

Koprivnica, Croatia
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Potocnjak I.,University of Rijeka | Broznic D.,University of Rijeka | Kindl M.,University of Zagreb | Kropek M.,BELUPO Pharmaceuticals Inc. | And 2 more authors.
Food and Chemical Toxicology | Year: 2017

We investigated the effect of natural sweetener Stevia rebaudiana and its constituent stevioside in cisplatin (CP)-induced kidney injury. Male BALB/cN mice were orally administered 10, 20, and 50 mg/kg body weight of Stevia rebaudiana ethanol extract (SE) or stevioside 50 mg/kg, 48 h after intraperitoneal administration of CP (13 mg/kg). Two days later, CP treatment resulted in histopathological changes showing kidney injury. Increased expression of 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and heme oxygenase-1 (HO-1) in mice kidneys suggested oxidative stress. CP treatment also increased renal expression of nuclear factor-kappaB (NF-κB) p65 subunit and phosphorylated inhibitor of NF-κB (IκBα), as well as expression of pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Induction of apoptosis and inhibition of the cell cycle in kidneys was evidenced by increased expression of p53, Bax, caspase-9, and p21, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), with concomitant suppression of Bcl-2 and cyclin D1 expression. The number of apoptotic cells in kidneys was also assessed. CP administration resulted in activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3). Both SE and stevioside attenuated CP nephrotoxicity by suppressing oxidative stress, inflammation, and apoptosis through mechanism involving ERK1/2, STAT3, and NF-κB suppression. © 2017 Elsevier Ltd


Smetisko J.,BELUPO Pharmaceuticals Inc. | Miljanic S.,University of Zagreb
Journal of Pharmaceutical and Biomedical Analysis | Year: 2017

The purpose of this study was to develop a NIR spectroscopic method for assessment of drug dissolution from allopurinol immediate release tablets. Thirty three different batches of allopurinol immediate release tablets containing constant amount of the active ingredient, but varying in excipients content and physical properties were introduced in a PLS calibration model. Correlating allopurinol dissolution reference values measured by the routinely used UV/Vis method, with the data extracted from the NIR spectra, values of correlation coefficient, bias, slope, residual prediction determination and root mean square error of prediction (0.9632, 0.328%, 1.001, 3.58, 3.75%) were evaluated. The obtained values implied that the NIR diffuse reflectance spectroscopy could serve as a faster and simpler alternative to the conventional dissolution procedure, even for the tablets with a very fast dissolution rate (>85% in 15 minutes). Apart from the possibility of prediction of the allopurinol dissolution rate, the other multivariate technique, PCA, provided additional data on the non-chemical characteristics of the product, which could not be obtained from the reference dissolution values. Analysis on an independent set of samples confirmed that a difference between the UV/Vis reference method and the proposed NIR method was not significant. According to the presented results, the proposed NIR method may be suitable for practical application in routine analysis and for continuously monitoring the product's chemical and physical properties responsible for expected quality. © 2017 Elsevier B.V.


Litvic M.,BELUPO Pharmaceuticals Inc. | Vecenaj I.,BELUPO Pharmaceuticals Inc. | Ladisic Z.M.,BELUPO Pharmaceuticals Inc. | Lovric M.,BELUPO Pharmaceuticals Inc. | And 2 more authors.
Tetrahedron | Year: 2010

For the first time hexaaquaaluminium(III) tetrafluoroborate has been used as a mild acid catalyst in organic synthesis. A simple method of its preparation based on the reaction of aluminium triisopropoxide and tetrafluoroboric acid in isopropanol afforded catalyst of high purity and activity. The three-component Biginelli condensation of acetoacetate esters, urea and aldehydes catalyzed by 10 mol % of [Al(H2O)6](BF4)3 in refluxing acetonitrile afforded 3,4-dihydropyrimidonones in good to high yields on multigram scales. The tolerance to acid sensitive reactants such as thienyl and furyl carbaldehydes, applicability to sterically hindered β-ketoesters and simple recyclability without losing catalytic activity make this catalyst as good replacement to literature methods. The mechanism of the reaction includes formation of the so called 'ureido-crotonate' rather than corresponding acylimino intermediate as found with Brønsted type catalysts. © 2010 Elsevier Ltd. All rights reserved.


Litvic M.,BELUPO Pharmaceuticals Inc. | Smic K.,BELUPO Pharmaceuticals Inc. | Vinkovic V.,Ruder Boskovic Institute | Filipan-Litvic M.,BELUPO Pharmaceuticals Inc.
Journal of Photochemistry and Photobiology A: Chemistry | Year: 2013

Photodegradation of rosuvastatin calcium (1) under several radiation wavelengths in solid state and solution in solvents of different polarity has been studied. It was shown that 1 is very sensitive, especially in solution, even to low energy wavelengths and main and almost exclusive degradation pathway includes formation of diastereomeric dihydrophenanthrene derivatives (R,S,R)-2 and (S,S,R)-2. Absolute configurations of isolated diastereomeric photoproducts in forms of respective lactones 3 and 4 have been determined. First partial diastereoselective photocyclization of 1 leading 10.5% d.e. of (R,S,R)-2 over (S,S,R)-2 has been determined in water as a solvent. To prevent photodegradation of 1 in solution use of brown glass is necessary. Solid formulations of 1 are efficiently protected against photodegradation by the presence of combination of dyes such as yellow iron oxide and pink color E122 or β-carotene inside the formulation or tablet coating. © 2012 Elsevier B.V.


Kolarovic D.L.,BELUPO Pharmaceuticals Inc. | Vinkovic V.,Ruder Boskovic Institute | Litvic M.,BELUPO Pharmaceuticals Inc.
Arkivoc | Year: 2016

A mild, highly efficient synthetic method was developed for the dehydrogenation of 3,4-dihydropyrimidin-2(1H)-ones employing in situ formed tert-butyl hypoiodite under basic conditions. The oxidant was prepared by the reaction of molecular iodine and potassium tertbutoxide. The reaction was carried out in dry tetrahydrofuran at room temperature and high purity products were isolated in high yields after simple work-up. The reaction times (3-10 min.) indicated the new method is superior in comparion to other literature oxidants employed under classical conditions or microwave promoted reactions. Two plausible mechanisms of dehydrogenation were proposed and the active species tert-butyl hypoiodite was characterized by UV/Vis spectroscopy method. ©ARKAT-USA, Inc.


Litvic M.,BELUPO Pharmaceuticals Inc. | Regovic M.,BELUPO Pharmaceuticals Inc. | Smic K.,BELUPO Pharmaceuticals Inc. | Lovric M.,BELUPO Pharmaceuticals Inc. | And 2 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2012

Mo(VI) and Mo(V) salts both react selectively with Hantzsch esters to produce substitute pyridines in good-to-excellent yield (75-99%). The remarkable reactivity and selectivity of MoOCl4 under reflux of acetonitrile and MoCl5 in dichloromethane at room temperature encouraged us to propose that molybdenum-containing enzymes (such as xanthine or aldehyde oxidase) also participate to some degree in the metabolism of 1,4-dihydropyridine drugs in the liver analogous to NADH in the respiratory chain. © 2012 Elsevier Ltd. All rights reserved.


PubMed | BELUPO Pharmaceuticals Inc.
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2012

Mo(VI) and Mo(V) salts both react selectively with Hantzsch esters to produce substitute pyridines in good-to-excellent yield (75-99%). The remarkable reactivity and selectivity of MoOCl(4) under reflux of acetonitrile and MoCl(5) in dichloromethane at room temperature encouraged us to propose that molybdenum-containing enzymes (such as xanthine or aldehyde oxidase) also participate to some degree in the metabolism of 1,4-dihydropyridine drugs in the liver analogous to NADH in the respiratory chain.

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