Biokomplex – szérum protein kölcsönhatások vizsgálata = Biocomplex – serum protein interactions

Antidiabetikus fémkomplexek Modelszámításokkal igazoltuk, a V(IV) és V(V) számára a transzferrin at elsődleges fémionkötőhely a vérszérumban. Mindkét fémiont képes kiszorítani komplexeiből, és bár az eredeti VO(IV) komplexek kötődnek egy másik szérumfehérjéhez az albuminhoz is, ez a köcsönhatás nem elég erős ahhoz, hogy megakadályozza a komplexek elbomlását. Mindez alátámasztja, hogy a fémion önmagában az aktív metabolit, és komplexképződéssel aktivitását nem lehet befolyásolni, legfeljebb a felszívódás hatékonyságát elősegíteni. Hasonló modellszámítások alapján megállapítottuk, hogy a Humán szérumalbumin a legfontosabb Zn(II) ion kötőhely a vérszérumban. ugyanazen fehérje képes megkötni számos ligandumot önmagában is. Rákellenes tioszemikarbazon komplexek Bár a triapin meglehetősen stabilis komplexek képez Fe(III)-mal, Ga(III) komplexe híg vizes oldatban jelentős mértékben hidrolizál. A stabiliás növekedést sikerül elérni szalicilaldehid alkalmazásával, ebben az esetben azonban a biológiai aktivitás csökken, ennek oka lehet a a hatásmechanizmus szempontjából fontos Fe(II)-komplexek kisebb stabilitása. Ruténium(II/III) komplexek A Ru(III)edta és Ru(II)-p-cimol bidentát ligandumokkal alkot terner komplexeinek stabilitása jelentősen növekszik ha a ligandum (S,O) és nem (O,O) vagy (N,O) donorcsoportokat tartalmaz. Ezt mindenképp érdemes figyelembe venni a gyógyszertervezési és a lehetséges biotranszformációs folyamatok esetében. | Antidiabetic metal complexes Based on model calculations, it can be stated that in the human serum transferrin is the primary V(IV,V) binder. The protein is able to displace the original carrier ligands for both meal ions. The other serum protein, albumin is also able to bind the V(IV,V) complexes, this interaction is not strong enough to prevent the dissociation of the complexes due to binding to transferrin. All these facts confirm that the metal ion itself is the active metabolite. By complex formation it’s activity cannot be tuned only the bioavailability can be increased. Similar model calculations confirmed that in the case of Zn(II) albumin (HSA) is the primary binder in the human serum. The same protein is able to bind the carrier ligands too. Anticancer tiosemicarbazone complexes Triapin forms high stability complexes with both Fe(II, III), but its Ga(III) complexes hydrolyze extensively in dilute water solutions. We were able to increase the stability by using salicilaldehyde-tiosemicarbazone, however in this case the anticancer activity decreased, probably due to the decreased stability of the Fe(II) complex, which has an important role in the mechanism of action. Ruthenium(II/III) complexes Ru(III)edta and Ru(II)p-cimol terner complexes with bidentate ligands are much more stable in the case of (S,O) type ligands as (O,O) or (N,O) type ligands. These facts should be considered during drug design and their potential biotransformation processes

Analysis of new synthetic cannabinoid in human urine by LC-MS/MS

Synthetic cannabinoids (SCs) are a group of novel psychoactive substances, which bind to cannabinoid receptors (CB1 and CB2). One of the largest groups of SCs are smoking mixtures, which are intended as legal replacements of cannabis and distributed on the illicit drug market. In 2016, 11 new SCs were reported by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The most commonly used techniques for quantitation of SCs in urine are high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). In this study we analysed in 2016-2017 released 6 new SCs such as 5F-MN18, AMB-CHMINACA, AMB-FUBINACA, APP-CHMINACA, CUMYL-4CNBINACA and THJ-2201. The LC-MS/MS system was optimised and the mass of identified parent ions, daughter ions and related retention time were determined. Matrix effect, extraction recovery and process efficiency were evaluated by the method proposed by Matuszewski et al

Identification of the main metabolites of three synthetic cannabinoids using LC-MS/MS technique

The consumption of designer drugs today is a serious problem, especially among young people involvement. ‘Herbal mixtures’ containing synthetic cannabinoids (SCs) that mimic the effect of marijuana and there are easily available via the Internet. For analysis of urine samples, knowledge of the main metabolites is necessary as the mother compounds are usually not found in urine after using, due to their fast metabolism. The aims of this study were the in vitro identification of metabolites of ADB-FUBINACA, 5F-MDMB-PICA and CUMYL-PEGACLONE and to determine which analytical targets are excreted into urine. Metabolites identified after incubation of SCs with pooled human liver microsomes (HLM). The authentic urine samples were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for investigation of the major in vivo metabolites. The main metabolites were the mono-hydroxylation of ADB-FUBINACA and CUMYL-PEGACLONE in positive urine specimens. We didn’t have positive sample of 5F-MDMB-PICA

Two hydroxy pyridinecarboxylic acid derivatives as a possible chelating agents in neurodegenerative disease; equilibrium complexation studies with Cu(II), Zn(II).

The metal ion chelators 4-hydroxy-5-methyl-3-pyridinecarboxylic acid (DQ5) and 1,5-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ715) and Cu(II) and Zn(II) were investigated with the aim to restore the homeostasis of the brain Cu(II) and Zn(II) in neurodegenerative diseases. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, and spectral (UV–Vis and EPR or 1H NMR) methods. The results show that in slightly acidic and neutral pH range mono and bis complexes are formed through bidentate coordination of the ligands. The biological MTT-test reveals that the DQ715 ligand is able to lower the cytotoxic effect of Cu(II) in human embryonic kidney HEK-293 cells. Our studies revealed, however, that none of the chelators were efficient enough to withdraw these metal ions from the amyloid aggregates

Módszerfejlesztés szintetikus kannabinoidok kimutatására vizeletből = Method development for determination of some new synthetic cannabinoid drugs from urine

The continuously increasing number of synthetic cannabinoids requires continuous method development for their determination in biological fluids. The aim of this work was to develop a reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of 13 synthetic cannabinoids (5F-AMBICA, AB-FUBINACA, AB-PINACA, AB-CHMINACA, ADB-CHMINACA, 5F-MDMB-PINACA, JWH-250, JWH-073, MDMB-CHMICA, JWH-078, AKB-48F, JWH-122, JWH-210) in human urine samples

Laboratory challenges of detecting synthetic cannabinoids in urine samples - a new sample preparation method

Synthetic cannabinoids (SCs) put the spotlight on the designer drugs’ market due to their dangerous – in some cases lethal – biological effects and easy accessibility. They are more potent than the well-known Δ⁹-tetrahydrocannabinol (THC) thanks to their special pharmacodynamic properties. The number of novel SCs on the market and of their users is growing which urges the forensic laboratories to use precise SCs detection methods routinely. Our aim was to develop a new sample preparation method for the newest 24 SCs analysis in urine samples achieving high recovery of SCs. Ethyl acetate was used instead of the traditional acetonitrile, and the targeted analysis of SCs was performed by use of liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-MS/MS) method. The related matrix effect and process efficiency of sample preparation method were taken in consideration as well in our study