Compound Profiling Laboratory

Budapest, Hungary

Compound Profiling Laboratory

Budapest, Hungary
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Muller J.,Budapest University of Technology and Economics | Esso K.,Corvinus University of Budapest | Dargo G.,Budapest University of Technology and Economics | Konczol A.,Compound Profiling Laboratory | Balogh G.T.,Compound Profiling Laboratory
European Journal of Pharmaceutical Sciences | Year: 2015

Due to its robustness and versatility, several variations of the blood-brain barrier specific parallel artificial membrane permeability assay (PAMPA-BBB) have been reported in the central nervous system (CNS) drug discovery practice. In this study, the impact of the main assay parameters on the predictive power of PAMPA-BBB was thoroughly investigated with 27, passively BBB-transported drug molecules with in vivo logBB data. The single and combined effects of the following variables were systematically studied and optimized: incubation time and temperature (4 vs. 18 h, RT vs. 37°C), type of the read-out (UV-reader vs. HPLC), solvent composition (n-dodecane/n-hexane), lipid concentration (0-10 w/v % PBLE), cholesterol content (0-1.66 w/v %), and thickness of the lipid membrane, and the DMSO cosolvent content (5-20 v/v %), respectively. Based on our results, solvent-driven and lipid-driven mechanisms of diffusion were identified in different assay conditions. Moreover, the analysis of membrane retention (MR%; the mole fraction of solute "lost" to the membrane) data obtained at various membrane compositions (volume of solvent and concentration of phospholipids) revealed the compound-specific nature of this parameter. The optimized conditions for the PAMPA-BBB were the following: 4 h incubation at 37°C, detection by HPLC-DAD, iso-pH conditions (pH = 7.4) with 5 v/v % DMSO content in buffer solutions, and PBLE (10 w/v %; without cholesterol) as membrane dissolved in the mixture of n-hexane:n-dodecane 3:1. © 2015 Elsevier B.V.All rights reserved.


Muller J.,Compound Profiling Laboratory | Martins A.,University of Szeged | Csabi J.,University of Szeged | Fenyvesi F.,Debrecen University | And 3 more authors.
European Journal of Pharmaceutical Sciences | Year: 2017

The anticancer potential of ecdysteroids, especially their chemo-sensitizing activity has recently gained a substantial scientific interest. A comprehensive physicochemical profiling was performed for a set of natural or semi-synthetic ecdysteroids (N = 37) to identify a lead compound against central nervous system (CNS) tumors. Calculated properties, such as lipophilicity (clogP), topological polar surface area (TPSA), brain-to-plasma ratio (clogBB) along with the measured blood-brain barrier specific in vitro permeability (logPe) were evaluated in parallel. Compounds with the highest CNS-availability predicted (clogBB > 0.0 and logPe > − 6.0) showed moderate to high lipophilicity (clogP = 3.89 − 5.25), relatively low TPSA (94.45 Å2), and shared a common apolar 2,3- and 20,22-diacetonide motif (25, 30–33). These ecdysteroids were selected for testing their capacity to sensitize SH-SY5Y neuroblastoma cells to vincristine. All of the five tested compounds exerted a remarkably strong, dose dependent chemo-sensitizing activity: at 2.5–10.0 μM ecdysteroids increased the cytotoxic activity of vincristine one to three orders of magnitude in (e.g., from IC50 = 39.5 ± 2.9 nM to as low as 0.056 ± 0.03 nM). Moreover, analysis of the combination index (CI) revealed outstanding synergism between ecdysteroids and vincristine (CI50 = 0.072 − 0.444). Thus, based on drug-likeness, physchem character and in vitro CNS activity, compound 25 was proposed as a lead for further in vivo studies. © 2016 Elsevier B.V.


Nemeth T.,Budapest University of Technology and Economics | Levai S.,Compound Profiling Laboratory | Kormos A.,Budapest University of Technology and Economics | Kupai J.,Budapest University of Technology and Economics | And 3 more authors.
Chirality | Year: 2014

The enantiomeric separation ability of the newly prepared chiral stationary phases containing acridino-18-crown-6 ether selectors was studied by high-performance liquid chromatography (HPLC). The chiral stationary phases separated the enantiomers of selected protonated primary aralkylamines efficiently. The best results were found for the separation of the mixtures of enantiomers of NO2-PEA. Chirality 26:651-654, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.


PubMed | Compound Profiling Laboratory, Spectroscopic Research and Budapest University of Technology and Economics
Type: | Journal: Journal of pharmaceutical and biomedical analysis | Year: 2016

The linkage between the central nervous system availability and neuropharmacological activity of the constituents of Ginkgo biloba L. extracts (GBE) is still incomplete. In this study, the in vitro blood-brain barrier (BBB) permeability profile of the standardised GBE was investigated by the parallel artificial membrane permeability assay (PAMPA). Biomarkers, such as terpene trilactones, flavonoid aglycones and ginkgotoxin exerted moderate or good BBB-permeability potential (BBB+), while glycosides and biflavones were predicted as unable to pass the BBB. N-methyltyramine (NMT) and N,N-dimethyltyramine or hordenine (Hor) were identified among BBB+ compounds, while subsequent direct HRMS analysis revealed tyramine (Tyr) and N,N,N-trimethyltyramine or candicine (Can) in GBE as trace constituents. Distribution of Tyr, NMT, Hor and Can was determined by a validated ion-exchange mechanism-based liquid chromatography-electrospray ionisation-mass spectrometry (LC-ESI-MS) method in G. biloba samples, such as herbal drugs and dietary supplements. The total content of the four tyramine derivatives in various GBEs ranged from 7.3 up to 6357g/g dry extract with NMT and Hor as most abundant ones. Considering the pharmacological activities and the revealed fluctuation in the concentration of the analysed adrenergic protoalkaloids, the presented rapid LC-ESI-MS method is proposed for monitoring of the levels of Tyr, NMT, Hor and Can in G. biloba products.


PubMed | Compound Profiling Laboratory, Budapest University of Technology and Economics and Semmelweis University
Type: Journal Article | Journal: Biomedical chromatography : BMC | Year: 2016

Feverfew (Tanacetum parthenium L., Asteraceae) is a perennial medicinal plant which has been used to alleviate the symptoms of migraine, headache and rheumatoid arthritis and possesses numerous pharmacological activities. An ultra-high-performance supercritical fluid chromatographic method (UHPSFC) was developed and validated in accordance with the International Conference on Harmonization guidelines in order to determine the camphor content of the volatile oil, which was accurate, precise, robust and selective. The method was validated for specificity, accuracy (100.2%), repeatability and intermediate precision, linearity (r


PubMed | Compound Profiling Laboratory, Budapest University of Technology and Economics and Corvinus University of Budapest
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2015

Due to its robustness and versatility, several variations of the blood-brain barrier specific parallel artificial membrane permeability assay (PAMPA-BBB) have been reported in the central nervous system (CNS) drug discovery practice. In this study, the impact of the main assay parameters on the predictive power of PAMPA-BBB was thoroughly investigated with 27, passively BBB-transported drug molecules with in vivo logBB data. The single and combined effects of the following variables were systematically studied and optimized: incubation time and temperature (4 vs. 18h, RT vs. 37C), type of the read-out (UV-reader vs. HPLC), solvent composition (n-dodecane/n-hexane), lipid concentration (0-10w/v % PBLE), cholesterol content (0-1.66w/v %), and thickness of the lipid membrane, and the DMSO cosolvent content (5-20v/v %), respectively. Based on our results, solvent-driven and lipid-driven mechanisms of diffusion were identified in different assay conditions. Moreover, the analysis of membrane retention (MR%; the mole fraction of solute lost to the membrane) data obtained at various membrane compositions (volume of solvent and concentration of phospholipids) revealed the compound-specific nature of this parameter. The optimized conditions for the PAMPA-BBB were the following: 4h incubation at 37C, detection by HPLC-DAD, iso-pH conditions (pH=7.4) with 5v/v % DMSO content in buffer solutions, and PBLE (10w/v %; without cholesterol) as membrane dissolved in the mixture of n-hexane:n-dodecane 3:1.


Balogh G.T.,Compound Profiling Laboratory | Muller J.,Budapest University of Technology and Economics | Konczol A.,Compound Profiling Laboratory
European Journal of Pharmaceutical Sciences | Year: 2013

In the present study we validated a widely used, high-throughput in vitro permeability model (PAMPA) to be used at the early stage of drug discovery for the phospholipidosis (PLD) prediction of drug-like compounds. Regarding the mechanism of action of PLD, our pH-gradient PAMPA system is the first noncell based model to mimic one-way transport of cationic amphiphilic drugs (CADs) from cytosol to the lysosome. Moreover, due to the fact that PLD can mainly occur in lung, liver, brain, kidney and heart, we have used similar commercially available original tissue-derived lipid fractions (heart, liver, brain), and in the case mimicking membrane of kidney and lung tissue we prepared tissue-mimetic artificial lipid mixtures in house. Metabolism of a drug can change the degree of PLD depending on the physicochemical properties of metabolites and the rate of metabolism. Our data from 57 drugs and 4 metabolites of earlier and 2 metabolites of newly recognized outliers (phenacetin and bupropion) using our pH-gradient PAMPA system show a good correlation with in vivo PLD data. Moreover, predictive ability of our best system, the lung specific pH-gradient PAMPA model was significantly better than widely used in silico models and it was also slightly better than that of the known noncell based models on our selection of compounds. Our pH-gradient PAMPA systems therefore offer mechanistically alternative, accurate and cost-effective screening tools for the early prediction of PLD potential of drug-like compounds. © 2013 Elsevier B.V. All rights reserved.


PubMed | Ocsa Bird Ringing Station, Compound Profiling Laboratory, Szent Istvan University, University of Szeged and Debrecen University
Type: | Journal: Scientific reports | Year: 2016

Ecdysteroids are important hormones that regulate moulting in arthropods. Three-host ixodid ticks normally moult to the next stage after finishing their blood meal, in the off-host environment. Presumably, three-host ticks that feed on the blood of insectivorous vertebrate hosts can be exposed to high levels of exogenous ecdysteroids causing them to initiate apolysis (the first step of moulting) on the vertebrate host. The aim of the present study was to investigate whether ticks undergo apolysis on insectivorous song birds, and if this phenomenon is associated with the seasonal variation in the availability of moths and with the presence of naturally acquired ecdysteroids in avian blood. During a triannual survey, 3330 hard tick larvae and nymphs were collected from 1164 insectivorous song birds of 46 species. A noteworthy proportion of ticks, 20.5%, showed apolysis. The occurrence of apolytic ticks on birds was correlated with the known seasonality of lepidopteran caterpillars. In addition, 18 blood samples of tick-infested birds were analysed with liquid chromatography - tandem mass spectrometry. Eight samples contained ecdysteroids or their derivatives, frequently in high concentrations, and the presence of these was associated with tick apolysis. In conclusion, naturally acquired ecdysteroids may reach high levels in the blood of insectivorous passerine birds, and will affect ticks (feeding on such blood) by shortening their parasitism.


PubMed | Compound Profiling Laboratory, University of Szeged and Debrecen University
Type: | Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences | Year: 2016

The anticancer potential of ecdysteroids, especially their chemo-sensitizing activity has recently gained a substantial scientific interest. A comprehensive physicochemical profiling was performed for a set of natural or semi-synthetic ecdysteroids (N=37) to identify a lead compound against central nervous system (CNS) tumors. Calculated properties, such as lipophilicity (clogP), topological polar surface area (TPSA), brain-to-plasma ratio (clogBB) along with the measured blood-brain barrier specific in vitro permeability (logP


Riethmuller E.,Semmelweis University | Riethmuller E.,Compound Profiling Laboratory | Toth G.,Semmelweis University | Alberti A.,Semmelweis University | And 5 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2015

Corylus maxima Mill. (Betulaceae) leaves have been used in traditional medicine both internally and externally, nevertheless phytochemical exploration of the plant remains incomplete. In this study, the in vitro antioxidant activity and polyphenolic composition of the ethyl acetate and methanolic extracts of C. maxima leaves and bark are reported for the first time. The radical scavenging activities of the extracts were investigated by the ABTS and DPPH assays. All the extracts of C. maxima possessed notable antioxidant activity. By mean of a HPLC-DAD-ESI-TOF and a HPLC-DAD-ESI-MS/MS method, altogether twenty-two phenolics were tentatively characterised: one flavan derivative (. 1), seven flavonol derivatives (. 4, 6, 12, 13, 16, 20 and 21) and fourteen diarylheptanoids (. 2, 3, 5, 7-. 11, 14, 15, 17-. 19 and 22). The amount of the two main flavonoids - myricetin-3-. O-rhamnoside (. 6) and quercetin-3-. O-rhamnoside (. 13) - and two diarylheptanoids - oregonin (. 3) and hirsutenone (. 15) - in the extracts were determined by a validated HPLC-ESI-MS/MS method in multiple reaction monitoring (MRM) mode. Our results showed that C. maxima could be considered as a valuable source of pharmacologically important natural products that might contribute to the revaluation of the phytotherapeutical potential of the plant. © 2014 Elsevier B.V.

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