LC-MS analysis of phenolic compounds and oleraceins in aerial parts of Portulaca oleracea L.

Portulaca oleracea L. (purslane) is a well-known edible and ethnomedicinal plant and it has been called “vegetable for long life” in the Chinese herbal medicine. The plant is recognized for the high content of polyphenols, including flavonoids and phenolic acids.In this study, hydromethanolic purslane extracts from Bulgarian and Greek locations were screened for polyphenolic content. Based on polyphenols, saponins and DPPH antioxidant activity, an orthogonaldesign L9(34) was performed in order to improve the ultrasound assisted extraction procedure of dry and fresh plant material. An UHPLC-Orbitrap-MS method in parallel-reaction monitoring mode was developed for the simultaneous identification and quantification of 14 compounds comprising hydroxybenzoic, hydroxycinnamic and caffeoylquinic acids, as well as 2 flavonol glycosides. The quantitative analysis was validated for curve fit, range, instrumental detection limit (IDL), instrumental quantification limit (IQL), LOD, LOQ, precision, recovery and accuracy. The UHPLC-MS quantification method revealed good linearity (r2 > 0.9950), LOD < 925.85 ng/g dw and LOQ < 3055.31 ng/g dw. Moreover, 11 cylco-dopa amides (Oleraceins A-D, N-Q, S, U and W) were tentatively identified through UHPLC-MS and their MS2 mass fragmentation was described

Role of the EMA specific marketing authorization procedures for early access on the time to patient access in Bulgaria

Despite the early access procedures for marketing authorization (MA) valid throughout the European Union still in the most of the Member states patient access to innovative medicines depends on cost-effectiveness, budget impact assessment and negotiations for price discount with the public payers. Retrospective analysis on the availability and time to market access of medicines authorized under the European medicines agency’s specific procedures for early access shows that despite the shortening of the time to market access after 2013, for most medicines still exceeds 365 days. This is due to the fact that requirements for pricing and reimbursement across EU is fixed to some degree and medicines with MA for early access are subject to the same legal requirements as the medicines with standard centralized marketing authorization. Some specific national legal requirements for pricing and reimbursement decisions, population of interest and manufactures intentions to enter certain markets should also be considered

<i>N</i>-[2-(1<i>H</i>-Indol-3-yl)ethyl]-2-(4-isobutylphenyl)propanamide

The compound in the title was prepared by reaction between tryptamine and ibuprofen using N,N&#8242;-dicyclohexylcarbodiimide as a &#8220;dehydrating&#8222; reagent. The structure of the newly synthesized compound was determined by nuclear magnetic resonance (NMR) (1H-NMR and 13C-NMR), UV, IR, and mass spectral data

Chemophenetic Approach to Selected Senecioneae Species, Combining Morphometric and UHPLC-HRMS Analyses

Herein, a chemophenetic significance, based on the phenolic metabolite profiling of three Senecio (S. hercynicus, S. ovatus, and S. rupestris) and two Jacobaea species (J. pancicii and J. maritima), coupled to morphometric data, is presented. A set of twelve morphometric characters were recorded from each plant species and used as predictor variables in a linear discriminant analysis (LDA) model. From a total 75 observations (15 from each of the five species), the model correctly assumed their species’ membership, except for 2 observations. Among the studied species, S. hercynicus and S. ovatus presented the greatest morphological similarity. A phytochemical profiling of phenolic specialized metabolites by UHPLC-Orbitrap-MS revealed 46 hydroxybenzoic, hydroxycinnamic, and acylquinic acids and their derivatives, 1 coumarin and 21 flavonoids. Hierarchical and PCA clustering applied to the phytochemical data corroborated the similarity of S. hercynicus and S. ovatus, observed in the morphometric analysis. This study contributes to the phylogenetic relationships between the tribe Senecioneae taxa and highlights the chemophenetic similarity/dissimilarity of the studied species belonging to Senecio and Jacobaea genera

Metamizole (dipyrone) – cytotoxic and antiproliferative effects on HeLa, HT-29 and MCF-7 cancer cell lines

Cancer pain treatment is a big challenge for healthcare providers and patients as well. The wide range of non-steroidal anti-inflammatory drugs (NSAIDs) used as painkillers in cancer patients, requires in-depth characterization of their effect on the disease process. The effects of NSAIDs have been widely studied over the last decades as preventive drugs in some oncological diseases. Metamizole is an NSAID belonging to the non-narcotic analgesics group and is highly recommended in oncology either alone or in combinations with opioid analgesics. There is a dearth of information regarding the cytotoxicity profile of metamizole and hence the present study evaluated the potential anticancer activity of metamizole in some permanent human tumour cell lines: HeLa, human cervical cancer cells; HT-29, a human colorectal adenocarcinoma cell line; and МСF-7, human breast adenocarcinoma cells. The studied tumour cells were sensitive to metamizole at doses higher than 25 μg/mL. Metamizole induced a statistically significant decrease in the viability of HeLa, HT-29 and MCF-7 cells in in vitro tests as measured by the MTT assay; the highest effect was observed at the 48th hour of the treatment. Metamizole could induce cell death by apoptosis. Metamizole also suppressed the migration of the three tumour cell lines. This was most clearly pronounced in HeLa cells. The results obtained indicate that metamizole is a suitable choice for the treatment of cancer pain and has prospects for further in-depth studies

UHPLC-Orbitrap screening of oleraindoles in hydromethanolic extracts of Portulaca oleracea

Purslane (Portulaca oleracea L., Portulacaceae) is a widespread edible plant with significant ethnobotanical and ethnopharmacological importance. The plant is characteristic for the presence of a class of indoline amide glucoside alkaloids, called cyclo-dopa amides, or oleraceins. Additionally, a new, structurally similar to oleraceins, class of indole amides have been discovered recently, called oleraindoles. These compounds have been evaluated to possess antiinflammatory and anticholinesterase activities. Herein, utilizing UHPLC-Orbitrap-MS with MS2 filtering by diagnostic ion filtering (DIF), and diagnostic difference filtering (DDF) using different data analysis tools, eight compounds with oleraindole structure were tentatively identified

An In-Depth Study of Metabolite Profile and Biological Potential of <i>Tanacetum balsamita</i> L. (Costmary)

Asteraceae species Tanacetum balsamita L. (costmary) is renowned for its traditional usage as an aromatic, carminative and tonic plant. This work aimed at in-depth study of the phytochemical and in vitro biological profilings of methanol–aqueous extracts from the costmary leaves, flower heads and roots. An UHPLC-HRMS analysis revealed more than 100 secondary metabolites including 24 acylquinic acids, 43 flavonoid glycosides, aglycones and methoxylated derivatives together with 15 phenolic acids glycosides. For the first time, 91 compounds are reported in the costmary. The flower heads extract possessing the highest content of total phenolics and flavonoids, actively scavenged DPPH (84.54 ± 3.35 mgTE/g) and ABTS radicals (96.35 ± 2.22 mgTE/g), and showed the highest reducing potential (151.20 and 93.22 mg TE/g for CUPRAC and FRAP, respectively). The leaves extract exhibited the highest inhibition towards acetyl- and butyrylcholinesterase (2.11 and 2.43 mg GALAE/g, respectively) and tyrosinase (54.65 mg KAE/g). The root extract inhibited α-glucosidase (0.71 ± 0.07 mmol ACAE/g), α-amylase (0.43 ± 0.02 mmol ACAE/g) and lipase (8.15 ± 1.00 mg OE/g). At a concentration >2 µg/mL, a significant dose dependent reduction of cell viability towards THP-1 monocyte leukemic cells was observed. Costmary could be recommended for raw material production with antioxidant and enzyme inhibitory properties

A new liquid chromatography-high resolution Orbitrap mass spectrometry-based strategy to characterize Glucuronide Oleanane-type Triterpenoid Carboxylic Acid 3, 28-O-Bidesmosides (GOTCAB) saponins.A case study of Gypsophila glomerata Pall ex M. B. (Caryophyllaceae)

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Design, Synthesis, In Silico Studies and In Vitro Evaluation of New Indole- and/or Donepezil-like Hybrids as Multitarget-Directed Agents for Alzheimer’s Disease

Alzheimer’s disease (AD) is considered a complex neurodegenerative condition which warrants the development of multitargeted drugs to tackle the key pathogenetic mechanisms of the disease. In this study, two novel series of melatonin- and donepezil-based hybrid molecules with hydrazone (3a–r) or sulfonyl hydrazone (5a–l) fragments were designed, synthesized, and evaluated as multifunctional ligands against AD-related neurodegenerative mechanisms. Two lead compounds (3c and 3d) exhibited a well-balanced multifunctional profile, demonstrating intriguing acetylcholinesterase (AChE) inhibition, promising antioxidant activity assessed by DPPH, ABTS, and FRAP methods, as well as the inhibition of lipid peroxidation in the linoleic acid system. Compound 3n, possessing two indole scaffolds, showed the highest activity against butyrylcholinesterase (BChE) and a high selectivity index (SI = 47.34), as well as a pronounced protective effect in H2O2-induced oxidative stress in SH-SY5Y cells. Moreover, compounds 3c, 3d, and 3n showed low neurotoxicity against malignant neuroblastoma cell lines of human (SH-SY5Y) and murine (Neuro-2a) origin, as well as normal murine fibroblast cells (CCL-1) that indicate the in vitro biocompatibility of the experimental compounds. Furthermore, compounds 3c, 3d, and 3n were capable of penetrating the blood–brain barrier (BBB) in the experimental PAMPA-BBB study. The molecular docking showed that compound 3c could act as a ligand to both MT1 and MT2 receptors, as well as to AchE and BchE enzymes. Taken together, those results outline compounds 3c, 3d, and 3n as promising prototypes in the search of innovative compounds for the treatment of AD-associated neurodegeneration with oxidative stress. This study demonstrates that hydrazone derivatives with melatonin and donepezil are appropriate for further development of new AChE/BChE inhibitory agents