Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

Jakab, Géza; Bogdán, Dóra; Mazák, Károly; Deme, Ruth; Mucsi, Zoltán; Mándity, István M.; Noszál, Béla; Kállai-Szabó, Nikolett; Antal, István

doi:10.1208/s12249-019-1525-6

Cited by 40 publications

(28 citation statements)

References 36 publications

(46 reference statements)

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“…Interestingly, no previous data can be found for RAMEB applying in phase-solubility studies of chrysin. In another work, with the flavone glycoside baicalin, where RAMEB was involved in the experiments, a similar order was reported for the stability constants: RAMEB > SBECD > HPBCD > βCD [25].…”

Section: Discussionsupporting

confidence: 69%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

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Chrysin is a bioflavonoid that can be found in natural products such as honey and propolis, and it possesses several biological effects such as antioxidant, anti-inflammatory, and anti-cancer activity. However, it is poorly soluble in water, and its bioavailability is limited. The aim of this research is to investigate the chrysin solubilization capacity of different β-cylcodextrin derivatives and compare their biological activities. Chrysin was complexed with β-cyclodextrin (βCD), hydroxypropyl-β-, (HPBCD) sulfobutylether-β-, (SBECD), and randomly-methylated-β-cyclodextrin (RAMEB) by the lyophilization method in 1:1 and 1:2 molar ratios. The solubilities of the chrysin–cyclodextrin complexes were tested, and the solubilization abilities of cyclodextrins were studied by phase solubility experiments. The cytotoxicity of the complexes was measured by the MTT method, and the permeability enhancement was tested on Caco-2 monolayers. The solubility study showed that the complexes formed with RAMEB had the highest solubility in water. The phase solubility experiments confirmed the strongest interaction between RAMEB and chrysin. In the viability test, none of the complexes showed cytotoxicity up to 100 µM concentration. The permeability study revealed that both at 1:1 and 1:2 ratios, the RAMEB complexes were the most effective to enhance chrysin permeability through the Caco-2 monolayers. In conclusion, cyclodextrins, especially RAMEB, are suitable for improving chrysin solubility and absorption.

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Section: Discussionsupporting

confidence: 69%

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

et al. 2020

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“…Initial pH values were read on a Metrohm 2.780.0010 precision pH meter with a 6.0258.600 Unitrode glass Pt 1000 electrode (Metrohm AG, Herisau, Switzerland). For the analysis of NMR titration curves of proton chemical shifts versus pH, the software Origin Pro 8 (OriginLab Corp., Northampton, MA, USA) was used [26] . Titrations were carried out the same way as in our previous publication [19] …”

Section: Methodsmentioning

confidence: 99%

“…For the analysis of NMR titration curves of proton chemical shifts versus pH, the software Origin Pro 8 (OriginLab Corp., Northampton, MA, USA) was used. [26] Titrations were carried out the same way as in our previous publication. [19]…”

Section: Nmr-ph Titrationsmentioning

confidence: 99%

Synthesis of 3‐O‐Carboxyalkyl Morphine Derivatives and Characterization of Their Acid‐Base Properties

Köteles

Mazák

Tóth

et al. 2021

Chemistry & Biodiversity

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The C-3 phenolic hydroxy group containing morphine derivatives (morphine, oxymorphone, naloxone, naltrexone) are excellent candidates for the synthesis of 3-O-functionalized molecules. Achieving free carboxylic group containing derivatives gives the opportunity for further modification and conjugation that could be used for immunization and immunoassays. For this purpose ethyl bromo-and chloroacetate can be used as O-alkylating agents. Hydrolyzing the products affords the appropriate free carboxylic group containing 3-O-carboxyalkyl derivatives. As these molecules contain an acidic and a basic functional group the protonation macro-and microconstants were determined too, using pH-potentiometry and NMR-pH titration, beside fully characterizing their structure using IR, CD, NMR and HR-MS measurements.

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“…The concentration of these indicators was 1.0 mM. For the analysis of NMR titration curves of proton chemical shifts versus pH, the software Origin Pro 8 (OriginLab Corp., Northampton, MA, USA) was used [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants

et al. 2020

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Vaccination could be a promising alternative warfare against drug addiction and abuse. For this purpose, so-called haptens can be used. These molecules alone do not induce the activation of the immune system, this occurs only when they are attached to an immunogenic carrier protein. Hence obtaining a free amino or carboxylic group during the structural transformation is an important part of the synthesis. Namely, these groups can be used to form the requisite peptide bond between the hapten and the carrier protein. Focusing on this basic principle, six nor-morphine compounds were treated with ethyl acrylate and ethyl bromoacetate, while the prepared esters were hydrolyzed to obtain the N-carboxymethyl- and N-carboxyethyl-normorphine derivatives which are considered as potential haptens. The next step was the coupling phase with glycine ethyl ester, but the reactions did not work or the work-up process was not accomplishable. As an alternative route, the normorphine-compounds were N-alkylated with N-(chloroacetyl)glycine ethyl ester. These products were hydrolyzed in alkaline media and after the work-up process all of the derivatives contained the free carboxylic group of the glycine side chain. The acid-base properties of these molecules are characterized in detail. In the N-carboxyalkyl derivatives, the basicity of the amino and phenolate site is within an order of magnitude. In the glycine derivatives the basicity of the amino group is significantly decreased compared to the parent compounds (i.e., morphine, oxymorphone) because of the electron withdrawing amide group. The protonation state of the carboxylate group significantly influences the basicity of the amino group. All of the glycine ester and the glycine carboxylic acid derivatives are currently under biological tests.

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Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes

Cited by 40 publications

References 36 publications

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Synthesis of 3‐O‐Carboxyalkyl Morphine Derivatives and Characterization of Their Acid‐Base Properties

Synthesis of Potential Haptens with Morphine Skeleton and Determination of Protonation Constants

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