Kratom Alkaloids: A Blood-Brain Barrier Specific Membrane Permeability Assay-Guided Isolation and Cyclodextrin Complexation Study.

Mitragynine is an "atypic opioid" analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability.

Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies.

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound.

From mother's milk to structural insights: H-N NMR analysis of Lewis X antigen-bearing oligosaccharides isolated from human milk.

Human milk oligosaccharides (HMOs) are complex unconjugated glycans abundant in breast milk, with vital roles in infant nutrition and health. The structural elucidation of HMOs remains challenging due to their diverse compositions and isomeric complexities. This study presents a novel approach employing H-N NMR correlations to pinpoint and characterize HMOs, LNH, LNnH, and their fucosylated derivatives including those of bearing the Lewis X motif.

Acid-sensitive prodrugs; a promising approach for site-specific and targeted drug release.

Drugs administered through conventional formulations are devoid of targeting and often spread to various undesired sites, leading to sub-lethal concentrations at the site of action and the emergence of undesired effects. Hence, therapeutic agents should be delivered in a controlled manner at target sites. Currently, stimuli-based drug delivery systems have demonstrated a remarkable potential for the site-specific delivery of therapeutic moieties.

Comprehensive Characterization of Phytochemical Composition, Membrane Permeability, and Antiproliferative Activity of Polyphenols.

The aim of our study was the detailed polyphenol profiling of and the characterization of the membrane permeability and antiproliferative properties of its main phenolics. A total of 161 compounds were tentatively identified in bark, leaf, and pericarp extracts by ultrahigh-performance liquid chromatography-high-resolution tandem mass spectrometry (UHPLC-HR-MS/MS). Eight compounds including myricetin-3--rhamnoside (), quercetin-3--rhamnoside (), quercetin-3--xyloside (), juglone (), 1,2,3,4-tetrahydro-7,8-dihydroxy-4-oxonaphthalen-1-yl-6--galloyl-glucoside (), ellagic acid (), gallic acid (), and ethyl gallate () were isolated from pericarp.

Solving the puzzle of 2-hydroxypropyl β-cyclodextrin: Detailed assignment of the substituent distribution by NMR spectroscopy.

2-Hydroxypropyl-β-cyclodextrin (HPBCD) is one of the most important cyclodextrin derivatives, finding extensive applications in the pharmaceutical sector. Beyond its role as an excipient, HPBCD achieved orphan drug status in 2015 for Niemann-Pick type C disease treatment, prompting research into its therapeutic potential for various disorders. However, the acceptance of HPBCD as an active pharmaceutical ingredient may be impeded by its complex nature.

Diterpenes Isolated from Three Different Species and Their Antiproliferative Activities against Gynecological and Glioblastoma Cancer Cells.

Fourteen diterpenes were isolated from methanol extracts of the aerial parts of, "Marginatus", and . The compounds belong to the abietane (-, -, and ), -clerodane (-), and -kaurane (, ) classes. Three new compounds were isolated from , including 3--acetylornatin G (), 3,12-di--acetylornatin G (), ornatin B methyl ester (), and ornatin F (), for which we proposed a revised structure.

Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs.

The characteristic alkaloid component of the leaves of the catnip shrub () is cathinone, and its synthetic analogs form a major group of recreational drugs. Cathinone derivatives are chiral compounds. In the literature, several chiral methods using cyclodextrins (CDs) have been achieved so far for diverse sets of analogs; however, a comprehensive investigation of the stability of their CD complexes has not been performed yet.

Anticholinesterase and Antityrosinase Secondary Metabolites from the Fungus .

is a widely distributed crust fungus reported from all continents except Antarctica, although considered a rare species in several European countries. Profound mycochemical analysis of the methanol extract of resulted in the isolation of seven compounds (-). Among them, (3β,22E)-3-methoxy-ergosta-4,6,8,22-tetraene () is a new natural product, while the NMR assignment of its already known epimer () has been revised.

Mixed β-γ-Cyclodextrin Branched Polymer with Multiple Photo-Chemotherapeutic Cargos.

The achievement of biocompatible platforms for multimodal therapies is one of the major challenges in the burgeoning field of nanomedicine. Here, we report on a mixed β- and γ-cyclodextrin-based branched polymeric material () covalently integrating a nitric oxide (NO) photodonor (NOPD) within its macromolecular scaffold, and its supramolecular ensemble with a singlet oxygen (O) photosensitizer (PS) Zn(II) phthalocyanine () and the chemodrug Lenvatinib (). This polymer is highly water-soluble and generates NO under visible blue light stimuli with an efficiency of more than 1 order of magnitude higher than that of the single NOPD.

Polyporenic Acids from the Mushroom Possess Chemosensitizing and Efflux Pump Inhibitory Activities on Colo 320 Adenocarcinoma Cells.

Polyporenic acids N-R (-), five novel 24-methylene lanostane triterpenes along with seven known polyporenic acids (-), were identified from the fruiting bodies of . The isolation of compounds - was performed by a combination of multistep flash chromatography and reversed-phase high-performance liquid chromatography (HPLC). The structure determination was carried out by extensive spectroscopic analysis, including 1D and 2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) experiments.

A Cyclodextrin Polymer as Supramolecular Matrix for Scalable Green Photooxygenation of Hydrophobic Substrates in Homogeneous Phase.

In the quest for new therapies targeting hypoxia, aromatic endoperoxides have intriguing potential as oxygen releasing agents (ORAs) able to free O in tissues upon suitable trigger. Four aromatic substrates were synthesized and the formation of their corresponding endoperoxides was optimized in organic solvent upon selective irradiation of Methylene Blue, a low-cost photocatalyst, producing the reactive singlet oxygen species. Complexation of the hydrophobic substrates within a hydrophilic cyclodextrin (CyD) polymer allowed their photooxygenation in homogeneous aqueous environment using the same optimized protocol upon dissolution in water of the three readily accessible reagents.

Utilizing the H-N NMR Methods for the Characterization of Isomeric Human Milk Oligosaccharides.

Human milk oligosaccharides (HMOs) are structurally complex unconjugated glycans that are the third largest solid fraction in human milk after lactose and lipids. HMOs are in the forefront of research since they have been proven to possess beneficial health effects, especially on breast-fed neonates. Although HMO research is a trending topic nowadays, readily available analytical methods suitable for the routine investigation of HMOs are still incomplete.

Fully Symmetric Cyclodextrin Polycarboxylates: How to Determine Reliable Protonation Constants from NMR Titration Data.

Acid-base properties of cyclodextrins (CDs), persubstituted at C-6 by 3-mercaptopropionic acid, sualphadex (Suα-CD), subetadex (Suβ-CD) and sugammadex (Suγ-CD, the antidote of neuromuscular blocking steroids) were studied by H NMR-pH titrations. For each CD, the severe overlap in protonation steps prevented the calculation of macroscopic p values using the standard data fitting model. Considering the full symmetry of polycarboxylate structures, we reduced the number of unknown NMR parameters in the "Q-fitting" or the novel "equidistant macroscopic" evaluation approaches.

Sugammadex analogue cyclodextrins as chiral selectors for enantioseparation of cathinone derivatives by capillary electrophoresis.

The present contribution describes the application of three single-isomeric cyclodextrin derivatives for the first time - Sugammadex, Subetadex and Sualphadex as chiral selectors. Their recognition ability was investigated by means of chiral capillary electrophoresis, on a pool of cathinone and amphetamine derivatives. The selectors differ in cavity sizes and in the number of ionizable groups which evidently influenced their enantioselectivity performance.

Analysis of 3-nitropropionic acid in Fabaceae plants by HPLC-MS/MS.

Introduction: 3-Nitropropionic acid (3-NPA) is a toxic compound that can accumulate in esterified form in the Fabaceae family. In the Lotae tribe, many species have been identified as 3-NPA producers (e.g.

High-performance thin-layer chromatography - antibacterial assay first reveals bioactive clerodane diterpenes in giant goldenrod (Solidago gigantea Ait.).

The present work introduces a high-performance thin-layer chromatography (HPTLC)-direct bioautography method using the Gram-positive plant pathogenic bacterium, Rhodococcus fascians. The screening and isolation procedure comprised of a non-targeted high-performance thin-layer chromatography-effect-directed analysis (HPTLC-EDA) against Bacillus subtilis, B. subtilis subsp.

Enantioseparation and quantitative determination of two homologous beta amino acids found in Fabaceae plants.

Non-protein amino acids are important metabolites of the Fabaceae family, possessing valuable biological effects in addition to their toxic properties. We have previously identified two non-protein amino acids homoproline and homopipecolic acid in Ononis species for the first time, and herein the study was extended to investigate further Fabaceae species (O. spinosa, O.

Characterization of alkaloid profile of L. and subsp. (Kreyer) Avet by LC-MS and NMR.

The alkaloid profile of L. and subsp. (Kreyer) Avet have not been characterized yet.

Sulfobutylation of Beta-Cyclodextrin Enhances the Complex Formation with Mitragynine: An NMR and Chiroptical Study.

Mitragynine (MTR), the main indole alkaloid of the well-known plant (), is one of the most studied natural products nowadays, due to its remarkable biological effects. It is a partial agonist on the opioid receptors, and as such relieves pain without the well-known side-effects of the opioids applied in the clinical practice. MTR and its derivatives therefore became novel candidates for drug development.

Enhancing the Anticancer Activity of Sorafenib through Its Combination with a Nitric Oxide Photodelivering β-Cyclodextrin Polymer.

In this contribution, we report a strategy to enhance the therapeutic action of the chemotherapeutic Sorafenib (SRB) through its combination with a multifunctional β-cyclodextrin-based polymer able to deliver nitric oxide (NO) and emit green fluorescence upon visible light excitation (PolyCDNO). The basically water-insoluble SRB is effectively encapsulated in the polymeric host (1 mg mL) up to a concentration of 18 μg mL. The resulting host-guest supramolecular complex is able to release SRB in sink conditions and to preserve very well the photophysical and photochemical properties of the free PolyCDNO, as demonstrated by the similar values of the NO release and fluorescence emission quantum efficiencies found.

In vitro and in silico evaluation of Ononis isoflavonoids as molecules targeting the central nervous system.

Isoflavonoids with various structural elements show a promising potential effect on central nervous system activities. Despite their favorable medicinal properties, the pharmacokinetic characteristics of this thoroughly investigated group of natural phenolics have only been described to a limited extent. Regarding the lack of information about the BBB permeability of isoflavones, isoflavanones, and pterocarpans found in Ononis species, the aim of our study was to investigate their physico-chemical properties influencing their absorption and distribution.

[The position of Ephedrae herba in the Western medicine].

Összefoglaló. A Magyar és az Európai Hypertonia Társaság legújabb ajánlásában a gyógyszer okozta szekunder hypertoniák gyakoribb okai között szerepel az Ephedra - csikófark (kínai nevén Mahuang) fajok drogjának (Ephedrae herba) felhasználása is. Összefoglaló közleményünk célja az Ephedra nemzetségbe tartozó, a gyógyászatban is felhasznált, a VIII.

Isolation and quantification of diarylheptanoids from European hornbeam (Carpinus betulus L.) and HPLC-ESI-MS/MS characterization of its antioxidative phenolics.

Detailed polyphenol profiling of European hornbeam (Carpinus betulus L.) bark, leaf, male and female catkin extracts was performed by high-performance liquid chromatography-diode array detection coupled to tandem mass spectrometry (HPLC-DAD-MS/MS). A total of 194 compounds were characterized and tentatively identified.

Molecular interactions in remdesivir-cyclodextrin systems.

Remdesivir (REM) is the first antiviral drug (Veklury™) approved by the Food and Drug Administration for the therapy of COVID-19. Due to its poor water solubility, the preparation of Veklury™ requires a suitable solubilizing excipient at pH 2 conditions. For this purpose, the final formulation contains the randomly substituted sulfobutylether-β-cyclodextrin (SBEβCD) as a complexing agent.