Electrospray Ionization Mass Spectrometry Analysis Research Articles

Label-free proteomics analysis on the envelope of budded viruses of Bombyx mori nucleopolyhedrovirus harboring differential localized GP64.

Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 is the key membrane fusion protein that mediates budded virus (BV) infection. We recently reported that BmNPV GP64's n-region of signal peptide (SP) blocked the SP-cleavage and mediated GP64 localization on the plasma membrane (PM); n-region (SP∆nGP64) absence caused GP64 intracellular localization, however, SP∆nGP64 was still incorporated into virion to generate BVs with lower infectivity. To better understand the biogenesis of the envelope of BmNPV BV, we conducted a label-free ESI mass spectrometry analysis of the envelope of purified BVs harboring PM localized GP64 or intracellular localized SP∆nGP64. The results indicated that 31 viral proteins were identified on the envelope, among which 15 were reported in other viruses. The other 16 proteins were first reported in BmNPV BV, including the BmNPV-specific protein BRO-A and proteins associated with vesicle transportation. Six proteins with significant intensity differences were detected in virions with differential localized GP64, and five specific proteins were identified in virions with GP64. Meanwhile, we identified 81 host proteins on the envelope, and seven lipoproteins were first identified in baculovirus virion; other 74 proteins are involved in the cytoskeleton, DNA-binding, vesicle transport, etc. In the meantime, eight and five specific host proteins were, respectively, identified in GP64 and SP∆nGP64's virions. The two virions shared 68 common host proteins, and 8 proteins were identified on their envelopes with a significant difference. This study provides new insight into the protein composition of BmNPV BV and a clue for further investigation of the budding mechanism of BmNPV.

Characterization of the surugamide biosynthetic gene cluster of TUA-NKU25, a Streptomyces diastaticus strain isolated from Kusaya, and its effects on salt-dependent growth.

Kusaya, a traditional Japanese fermented fish product, is known for its high preservability, as it contains natural antibiotics derived from microorganisms, and therefore molds and yeasts do not colonize it easily. In this study, the Streptomyces diastaticus strain TUA-NKU25 was isolated from Kusaya, and its growth as well as the production of antibiotics were investigated. Strain TUA-NKU25 showed advantageous growth characteristics in the presence, but not in the absence, of sodium chloride (NaCl). Antimicrobial assay, high-performance liquid chromatography, and electrospray ionization-mass spectrometry analysis showed that this strain produced surugamide A and uncharacterized antimicrobial compound(s) during growth in the presence of NaCl, suggesting that the biosynthesis of these compounds was upregulated by NaCl. Draft genomic analysis revealed that strain TUA-NKU25 possesses a surugamide biosynthetic gene cluster (sur BGC), although it is incomplete, lacking surB/surC. Phylogenetic analysis of strain TUA-NKU25 and surugamide-producing Streptomyces showed that sur BGC formed a clade distinct from other known groups.

Acidolysis of Poly(ethylene terephthalate) Waste Using Succinic Acid under Microwave Irradiation as a New Chemical Upcycling Method.

A novel method of chemical upcycling of used poly(ethylene terephthalate) (PET) bottles by acidolysis with succinic acid (SA) was performed under microwave irradiation. The long polyester chain of PET was efficiently fragmented into small molecules and oligomers, such as terephthalic acid and α,ω-dicarboxylic acid oligo(ethylene succinate-co-terephthalate) (OEST). Various input molar ratios of SA/PET from 1.0 to 2.5 were used, and the product mixtures were separated successfully. The recovered terephthalic acid can be reused as a basic chemical. The α,ω-dicarboxylic acid OEST was used as a curing agent for epoxy resin. The recovered SA can be reused for further PET acidolysis. Structures of OEST were identified by Fourier transform infrared (FTIR) spectroscopy, 1H NMR spectroscopy, and electrospray ionization-mass spectrometry (ESI-MS). The presence of succinic anhydride as a side product was confirmed by FTIR and ESI-MS analyses. The evaporation of SA and the formation of volatile succinic anhydride compete with the acidolysis of PET. The minimum SA/PET ratio of 1.0 was selected so that the acidolysis was effective and without the SA recovery step by MEK treatment. OEST-1.0 was used for curing diglycidyl ether of bisphenol A. The structures and thermal properties of cured adducts were confirmed by FTIR and differential scanning calorimetry (DSC). This chemical upcycling method of PET is eco-friendly without the use of a solvent and a catalyst for the reaction, and all materials were recovered and they could be reused for novel polymer preparation.

Enriching Chemical Space of Bioactive Scaffolds by New Ring Systems: Benzazocines and Their Metal Complexes as Potential Anticancer Drugs.

The search for new scaffolds of medicinal significance combined with molecular shape enhances their innovative potential and continues to attract the attention of researchers. Herein, we report the synthesis, spectroscopic characterization (1H and 13C NMR, UV-vis, IR), ESI-mass spectrometry, and single-crystal X-ray diffraction analysis of a new ring system of medicinal significance, 5,6,7,9-tetrahydro-8H-indolo[3,2-e]benzazocin-8-one, and a series of derived potential ligands (HL1-HL5), as well as ruthenium(II), osmium(II), and copper(II) complexes (1a, 1b, and 2-5). The stability of compounds in 1% DMSO aqueous solutions has been confirmed by 1H NMR and UV-vis spectroscopy measurements. The antiproliferative activity of HL1-HL5 and 1a, 1b, and 2-5 was evaluated by in vitro cytotoxicity tests against four cancer cell lines (LS-174, HCT116, MDA-MB-361, and A549) and one non-cancer cell line (MRC-5). The lead compounds HL5 and its copper(II) complex 5 were 15× and 17×, respectively, more cytotoxic than cisplatin against human colon cancer cell line HCT116. Annexin V-FITC apoptosis assay showed dominant apoptosis inducing potential of both compounds after prolonged treatment (48 h) in HCT116 cells. HL5 and 5 were found to induce a concentration- and time-dependent arrest of cell cycle in colon cancer cell lines. Antiproliferative activity of 5 in 3D multicellular tumor spheroid model of cancer cells (HCT116, LS-174) superior to that of cisplatin was found. Moreover, HL5 and 5 showed notable inhibition potency against glycogen synthase kinases (GSK-3α and GSK-3β), tyrosine-protein kinase (Src), lymphocyte-specific protein-tyrosine kinase (Lck), and cyclin-dependent kinases (Cdk2 and Cdk5) (IC50 = 1.4-6.1 μM), suggesting their multitargeted mode of action as potential anticancer drugs.

Discovery of natural polyphenols from the wild vegetable Suaeda salsa L. with potential cardioprotective functions

Suaeda salsa L. (Chenopodiaceae) is a wild vegetable distributed along the northern coast of China. Searching for potential agents with health benefits from S. salsa L. led to the identification of 14 flavonoids (1–14), eight phenolic acids (15–22), one coumarin (23), one benzoquinone (24), two sesquiterpenes (25, 26), and three lignins (27–29) from an aqueous ethanol (EtOH) extract of the above-ground whole plant using various column chromatographic methods. High-resolution electrospray ionization mass spectrometry (HRESIMS) analyses and nuclear magnetic resonance (1H and 13C NMR) spectroscopy were adopted to examine the structural properties of the compounds. To date, our study is the first to identify 20 compounds from this genus. Some compounds exhibited significant health benefits in zebrafish models. Compounds 2, 4, 23, and 28 significantly improved oxidative damage, while compounds 1–5, 7, 11, 13, 18, 19, and 23 significantly improved zebrafish lateral line neuromast inflammation. Additionally, compounds 1, 4, 8, 13, and 16 significantly promoted zebrafish angiogenesis, while compounds 3–5 and 18 significantly improved zebrafish arrhythmia. Furthermore, a flavonoid-targeted metabolomics study revealed that flavanone was the precursor of all of the flavonoids and had its highest accumulation in August, while the others showed their highest accumulation in September. Thus, the best time to harvest most of the bioactive polyphenols is during September. The present study revealed that the wild vegetable S. salsa L. might be developed as a potential cardioprotective functional food.

Evaluation of the Stability of Popular Oils for Fittura Through Analytical Techniques

ABSTRACT This study assessed the stability of commonly used frying oils submitted to a specific heat treatment. Gas chromatographic analysis (GC-FID) revealed a decrease in the content of polyunsaturated fatty acids (PUFAs) and production of linolelaidic acid (18: 2n-6t). Furthermore, electrospray ionization mass spectrometry (ESI-MS) analysis demonstrated that the triacylglycerol (TAG) content of molecules composed of linoleic acid (L), oleic acid (O), and linolenic acid (Ln) exhibited the greatest decrease during heating. Among the evaluated vegetable oils, soybean oil exhibited the lowest temperature of stability. Conversely, the lowest concentration of trans-fatty acids (TFA) was observed for canola oil.

Interaction of Atomically Precise Thiolated Copper Nanoclusters with Proteins: A Comparative Study.

A facile synthesis of glutathione-stabilized copper nanoclusters (CuNCs) is carried out in H2O/ tetrahydrofuran medium. The photophysical and morphological studies performed with as-synthesized CuNCs revealed the formation of green-emissive, stable, and smaller nanoclusters. The precise composition of these as-synthesized CuNCs was predicted with the aid of electrospray ionization mass spectrometry analysis as Cu12(SG)9. Furthermore, the systematic studies of the interaction of synthesized CuNCs with three plasmatic proteins, namely, bovine serum albumin (BSA), lysozyme (Lys), and hemoglobin (Hb) have been performed by using a series of spectroscopic studies. The conformational changes in these proteins upon interacting with CuNCs and their binding stoichiometries have been investigated from the combination of UV-visible and steady-state fluorescence measurements. The changes in the microenvironment of proteins caused by CuNCs were investigated by circular dichroism spectroscopy. Among these three proteins, BSA and Lys had a minor effect on the luminescence of CuNCs, which makes them suitable candidates for biological applications. There are no drastic changes in the microenvironment of NCs as well as proteins because of the possibilities of weak electrostatic and H-bonding interactions of CuNCs with BSA and Lys. The feasibility of strong metallophic interaction between the Fe2+ present in the heme group of Hb and Cu(I) or -S atoms present in the CuNCs brings considerable changes in the photophysical activity of CuNCs and their interactions with Hb. The functional groups on NCs as well as active amino acid residues present in proteins play a crucial role in determining their interactions. This work shed a piece of knowledge on designing NCs for specific biological applications.

Insights into the Complexation Mechanism of a Promising Lipophilic PyTri Ligand for Actinide Partitioning from Spent Nuclear Fuel.

The challenging issue of spent nuclear fuel (SNF) management is being tackled by developing advanced technologies that point to reduce environmental footprint, long-term radiotoxicity, volumes and residual heat of the final waste, and to increase the proliferation resistance. The advanced recycling strategy provides several promising processes for a safer reprocessing of SNF. Advanced hydrometallurgical processes can extract minor actinides directly from Plutonium and Uranium Reduction Extraction raffinate by using selective hydrophilic and lipophilic ligands. This research is focused on a recently developed N-heterocyclic selective lipophilic ligand for actinides separation to be exploited in advanced Selective ActiNide EXtraction (SANEX)-like processes: 2,6-bis(1-(2-ethylhexyl)-1H-1,2,3-triazol-4-yl)pyridine (PyTri-Ethyl-Hexyl-PTEH). The formation and stability of metal-ligand complexes have been investigated by different techniques. Preliminary studies carried out by electrospray ionization mass spectrometry (ESI-MS) analysis enabled to qualitatively explore the PTEH complexes with La(III) and Eu(III) ions as representatives of lanthanides. Time-resolved laser fluorescence spectroscopy (TRLFS) experiments have been carried out to determine the ligand stability constants with Cm(III) and Eu(III) and to better investigate the ligand complexes involved in the extraction process. The contribution of a 1:3 M/L complex, barely identified by ESI-MS analyses, was confirmed as the dominant species by TRLFS experiments. To shed light on ligand selectivity toward actinides over lanthanides, NMR investigations have been performed on PTEH complexes with Lu(III) and Am(III) ions, thereby showing significant differences in chemical shifts of the coordinating nitrogen atoms providing proof of a different bond nature between actinides and lanthanides. These scientific achievements encourage consideration of this PyTri ligand for a potential large-scale implementation.

Pomegranate Extract Affects Fungal Biofilm Production: Consumption of Phenolic Compounds and Alteration of Fungal Autoinducers Release.

Candida albicans expresses numerous virulence factors that contribute to pathogenesis, including its dimorphic transition and even biofilm formation, through the release of specific quorum sensing molecules, such as the autoinducers (AI) tyrosol and farnesol. In particular, once organized as biofilm, Candida cells can elude conventional antifungal therapies and the host's immune defenses as well. Accordingly, biofilm-associated infections become a major clinical challenge underlining the need of innovative antimicrobial approaches. The aim of this in vitro study was to assess the effects of pomegranate peel extract (PomeGr) on C. albicans growth and biofilm formation; in addition, the release of tyrosol and farnesol was investigated. The phenolic profile of PomeGr was assessed by high-performance liquid chromatography coupled to electrospray ionization mass spectrometry (HPLC-ESI-MS) analysis before and after exposure to C. albicans. Here, we showed that fungal growth, biofilm formation and AI release were altered by PomeGr treatment. Moreover, the phenolic content of PomeGr was substantially hampered upon exposure to fungal cells; particularly pedunculagin, punicalin, punicalagin, granatin, di-(HHDP-galloyl-hexoside)-pentoside and their isomers as well as ellagic acid-hexoside appeared highly consumed, suggesting their role as bioactive molecules against Candida. Overall, these new insights on the anti-Candida properties of PomeGr and its potential mechanisms of action may represent a relevant step in the design of novel therapeutic approaches against fungal infections.

Undescribed isoquinolines from Zanthoxylum nitidum and their antiproliferative effects against human cancer cell lines

Eleven previously undescribed alkaloids, including three pairs of enantiomers nitidumalkaloids A–C, a pair of scalemic mixtures nitidumalkaloid D and three optically pure or achiral alkaloids, nitidumalkaloids E–G, along with 20 known alkaloids, were isolated from an ethanolic extract of the whole Zanthoxylum nitidum (Roxb.) DC plant. The chemical structures of the alkaloids were elucidated using a combination of comprehensive nuclear magnetic resonance (NMR) and high-resolution electro-spray ionization mass spectrometry (HR-ESI-MS) analyses. The configuration of the stereogenic centers of all undescribed compounds was precisely established based on single-crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Racemic mixtures of nitidumalkaloids A–D were purified, and their enantiomers were analyzed via chiral-phase high-performance liquid chromatography with electrochemical detection measurements (HPLC-ECD). Twelve compounds exhibited significant antiproliferative activities against a panel of cancer cell lines. Further studies were designed to investigate the underlying molecular mechanism of (1′S, 6R)-nitidumalkaloid B, which was the most active antiproliferative agent against human cancer A549 cells. G2/M cell cycle arrest, induction of apoptosis, and suppression of the Wnt/β-catenin signaling pathway were in part associated with the antiproliferative activity of (1′S, 6R)-nitidumalkaloid B. Moreover, (1′S, 6R)-nitidumalkaloid B inhibited cell migration by downregulating the epithelial-mesenchymal transition process in A549 cells. These data suggest that the antiproliferation activity of (1′S, 6R)-nitidumalkaloid B was correlated with the stereoselectivity of the stereoisomers, and (1′S, 6R)-nitidumalkaloid B was prioritized as a potential leading compound for the management of aggressive human non-small-cell lung cancer (NSCLC) from natural products.

Lucy is back in Brazil with a new dress

Lucy in the Sky with Diamonds, a John Lennon song that was a hit in the 1960s, was born amidst a social context enlightened by lysergic acid diethylamide (LSD). In Brazil, both the drug and the song were very popular at the time, although it gradually mitigated. Nevertheless, while the song remains out of the spotlight, LSD derivatives are currently gaining attention with the rising of the new psychoactive substances (NPS). With this new presentation, the drug is returning to Brazil after a few decades and herein we report and discuss the first cases of an LSD prodrug seized in our country. Nine suspected blotter paper samples were seized by the Sao Paulo State Police in different cities of the State. Gas chromatography-mass spectrometry (GC-MS), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) and liquid chromatography coupled with electrospray ionization-mass spectrometry (LC-ESI-MS) analyses were utilized to confirm the identity of the LSD derivative. The compound was identified as 4-acetyl-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide (ALD-52 or 1A-LSD) and no other active substance was detected in all samples. The identity of the unknown compound found in seized blotter papers has been successfully confirmed as an LSD prodrug, ALD-52, which was not controlled by Brazilian legislation. The arrival of a new type of designer drug in Brazil is in support by other reports, although those are still scarce and should not be overlooked. Altogether, these findings indicate the rising of a new NPS strategy that merits proper discussion.

Chemical profiling of Dizygostemon riparius (Plantaginaceae) plant extracts and its application against larvae of Aedes aegypti L. (diptera: culicidae)

Dengue fever is a reemerging disease of global concern among health authorities due to its high rate of proliferation. In 2019, Brazil registered its second-highest dengue mortality rate since 1998, with approximately 754 deaths and 1.5 million probable cases. Brazilian Ministry of Health prevention and control strategies for Aedes include insecticides, eradication of breeding sites, and awareness campaigns. However, as new mosquito variants resistant to conventional insecticides emerge, there is an increasing demand for effective environment-friendly plant extracts and natural substances against adult mosquitos and/or larvae of Aedes aegypti L. with no negative impacts on human health. This study aimed to investigate the larvicidal activity of Dizygostemon riparius extracts and analyze its chemical profile for the first time. Dizygostemon is a Plantaginaceae bytipic genus and D. riparius is an aromatic plant recently identified in Maranhão, Brazil. The essential oil from its lilac morphotype already exhibited larvicidal potential against Aedes albopictus, but the still limited data on this new plant species require further chemical and biological studies on other species, such as Aedes aegypti. Ethyl acetate and methanol crude leaf extracts yielded, respectively, 17.60 and 25.96%. High-performance liquid chromatography (HPLC) with UV detection coupled with electrospray ionization mass spectrometry (HPLC-UV-ESI-IT/MS) analyses confirmed the presence of polymethoxyflavones and coumarins, such as isorhamnetin 3-galactoside-7-rhamnoside, 5,7-dihydroxy-3-(3-hydroxy-4,5-dimethoxyphenyl)-6-methoxy-4-benzopyrone and 3′,5-dihydroxy-4′,6,7-trimethoxyflavone. Ethyl acetate extract presented the best performance in larvicide bioassays (LC50 = 542.2 ± 11.5 µg.mL−1). Our results highlight the chemical and biological potential of this new species found in the cerrado of eastern Maranhão and open perspectives for future studies focusing on isolating and identifying other active secondary metabolites of Dizygostemon riparius.

Insecticidal characteristics and structural identification of the potential active compounds from Streptomyces sp. KR0006: Strain improvement through mutagenesis.

Pest control by biological means is an effective, eco-friendly, and promising method that typically involves compounds naturally derived from actinomycetes. Thus, the present study aimed to screen, characterize, and identify the structure of insecticidal compounds from Streptomyces sp. KR0006 and increase the activity through mutagenesis. In the examination of the insecticidal activity level of the isolates, Streptomyces sp. KR0006 metabolite showed significant activity against larvae and moths of Plutella xylostella. Taxonomic analyses of the 16S rRNA gene sequences revealed that the isolated KR0006 strain tended to be 99% consistent with Streptomyces cinereoruber strain NBRC 12756. Three active compounds isolated from the culture filtrate of KR0006 were purified by solvent partition, mid-pressure liquid chromatography (MPLC), Sephadex LH20 column chromatography, and high-performance liquid chromatography (HPLC). By performing 1H-NMR, 13C-NMR, and 2D-NMR experiments, and high-resolution electrospray ionization mass spectrometry analysis, the 316-HP2, 316-HP3, and 316-HP5 compounds were inferred as antimycin A3a (MW, 519.; C26H36N2O9), antimycin A8a (MW, 534; C27H38N2O9), and antimycin A1a (MW, 548; C28H40N2O9) respectively. Mutant U67 obtained from exposure to ultraviolet (UV) irradiation (254 nm, height 17 cm) for 70 seconds resulted in a 70% more larval mortality than that of the initial wild culture. The second mutation of the culture broth enhanced insecticidal activity by 80 and 100% compared with the first mutation and initial medium, respectively. Our study found that Streptomyces sp. KR0006 strain produces insecticidal active compounds and could be used for practical pest management.

Visible light‐triggered pyrazole‐functionalized reversible ionophore for selective monitoring of aluminium (III) ion

A photo‐switchable ionophore, (E)‐4‐([2‐hydroxy‐3‐methoxybenzylidene]amino)‐1,5‐dimethyl‐2‐phenyl‐1,2‐dihydro‐3H‐pyrazol‐3‐one (S1), was rationally designed and developed for the visible light‐triggered selective and efficient transport of Al (III) ions. The non‐fluorescent probe distinctly manifests its green light at 518 nm in presence of Al (III) ion upon irradiation at 405 nm and showed a turned‐off emission with EDTA in ethanol. The binding mode and structural perspective of S1 were assessed through X‐ray crystallography, spectrophotometry, spectrofluorimetry, 1H nuclear magnetic resonance (NMR) titration, electrospray ionization mass spectrometry (ESI‐MS) analysis and computational calculations, suggesting a 1:1 binding stoichiometry and a distorted tetrahedral coordination geometry of S1‐Al complex. The testing strip was also developed with S1 coating for colourimetric and naked‐eye detection of Al (III) ion as evident from the green fluorescence upon irradiation at 365 nm. Further, a bioimaging study of S1 in human colon living cells (HP‐29) revealed the presence of Al (III) ion through a bright green fluorescence in HP‐29, indicating the potentiality of S1 to trace Al (III) in living cells. Additionally, cytotoxicity studies by MTT assay and staining analysis ensured that the probe might be an efficient and sensitive chemosensor for monitoring Al (III) ion in drug delivery and biological applications.

New insights into the Van Krevelen diagram: Automated molecular formula determination from HRMS for a large chemical profiling of lichen extracts.

In recent years, LC-MS has become the golden standard for metabolomic studies. Indeed, LC is relatively easy to couple with the soft electrospray ionization. As a consequence, many tools have been developed for the structural annotation of tandem mass spectra. However, it is sometimes difficult to do data-dependent acquisition (DDA), especially when developing new methods that stray from the classical LC-MS workflow. An old tool from petroleomics that has recently gained popularity in metabolomics, the Van Krevelen diagram, is adapted for an overview of the molecular diversity profile in lichens through high-resolution mass spectrometry (HRMS). A new method is benchmarked against the state-of-the-art classification tool ClassyFire using a database containing most known lichen metabolites (n ≈2,000). Four lichens known for their contrasted chemical composition were selected, and extractions with apolar, aprotic polar, and protic polar solvents were performed to cover a wide range of polarities. Extracts were analyzed with direct infusion electrospray ionization mass spectrometry (DI-ESI-MS) and atmospheric solids analysis probe mass spectrometry (ASAP-MS) techniques to be compared with the chemical composition described in the literature. The most common lichen metabolites were efficiently classified, with more than 90% of the molecules in some classes being matched with ClassyFire. Results from this method are consistent with the various extraction protocols in the present case study. This approach is a rapid and efficient tool to gain structural insight regarding lichen metabolites analyzed by HRMS without relying on DDA by LC-MS/MS analysis. It may notably be of use during the development phase of novel MS-based metabolomic approaches.

Polyphenolic Glycosides from the Fruits Extract of Lycium ruthenicum Murr and Their Monoamine Oxidase B Inhibitory and Neuroprotective Activities.

The fruits ofLycium ruthenicum Murr have long been consumed as health food and used in folk medicine in China. Apart from the well-known polysaccharides, the active small molecular constituents in this fruit have not been fully studied. In this work, a systematic phytochemical study was carried out to investigate the small molecules and their potential health benefits. Nine new polyphenolic glycosides, lyciumserin A-I (1-9), together with 16 known compounds (10-25), were isolated and elucidated by high-resolution electrospray ionization mass spectrometry and comprehensive NMR analyses in combination with chemical hydrolysis. Compounds 1, 2, and 16 exhibited moderate inhibitory activity of monoamine oxidase B (MAO-B), while compounds 1 (50 μM) and 2 (100 μM) displayed significant neuroprotective effects (69.22 and 72.38% of cell viability, respectively) in the 6-hydroxydopamine-induced injury of the PC12 cell model (54.41%), comparable to the positive drug rasagiline (70.45%). The neuroprotective effect of 1 and 2 was further evidenced by the observation of the morphological change and fluorescein diacetate/propidium iodide staining. In addition, the levels of the major active compounds (1, 3, 5/6, and 16-18) vary from 21.5 to 892.3 μg/g. This is the first report on phenolic glycosides from the fruits ofL. ruthenicum Murr that possess both significant MAO-B inhibitory and neuroprotective effects, indicating the promising potential of the fruits for the development of health care products and even therapeutic agents for the treatment of Parkinson's disease and other neurodegenerative diseases.

Millet bran globulin hydrolysate derived tetrapeptide-ferrous chelate: Preparation, structural characterization, security prediction in silico, and stability against different food processing conditions

Through Sephadex gel chromatography, reverse-phase-high-performance-liquid-chromatography and ultra-high performance-liquid-chromatography coupled with electrospray ionization mass spectrometry analysis, a novel tetrapeptide (Ser-Glu-Leu-Glu) of excellent ferrous-chelating capacity (41.24 μmol/g) was identified in millet bran globulin hydrolysate. Physicochemical properties and security of SELE were predicted in silico. The result showed that SELE was no toxic. Based on a model generated from response surface methodology, the optimum preparation conditions of SELE-ferrous chelate were obtained with the mass ratio of SELE to FeCl2·4H2O of 43.3: 1, at pH 6.7 and 28.7 °C for 28.8 min. The ferrous-chelating ratio of SELE was 97.06% under these conditions. Structure of SELE-ferrous chelate was characterized with ultraviolet spectroscopy, Fourier-infrared spectroscopy and scanning electron microscope. The results demonstrated that amino group and carboxyl group of SELE were the primary ferrous-chelating sites. Moreover, SELE-ferrous chelate showed higher iron-solubility than FeCl2 and ferrous lactate against different pasteurization conditions, heating at 100 °C for 30 min, and various pH values (P < 0.05). SELE-ferrous chelate also demonstrated higher iron-solubility than FeCl2 and ferrous lactate against simulated gastrointestinal digestion (P < 0.05). These results indicated that SELE could be used as ingredient of iron fortifications and had potential applications in the food industry.

Elucidation of Structure-Activity Relationships in Indolobenzazepine-Derived Ligands and Their Copper(II) Complexes: the Role of Key Structural Components and Insight into the Mechanism of Action.

Indolo[3,2-d][1]benzazepines (paullones), indolo[3,2-d][2]benzazepines, and indolo[2,3-d][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-d][2]benzazepine-derived ligands HL1–HL4 and copper(II) complexes 1–4. All compounds were characterized by spectroscopic methods (1H and 13C NMR, UV–vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes 2 and 3, in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by 1H NMR and UV–vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure–activity relationships were deduced from the comparison of anticancer activities of HL1–HL4 and 1–4 with those of structurally similar paullone-derived (HL5–HL7 and 5–7) and latonduine-derived scaffolds (HL8–HL11 and 8–11). The high anticancer activity of the lead drug candidate 4 was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.

A New 'Off-On' System Based on Core-Substituted Naphthalene Diimide with Dimethylamine for Reversible Acid-Base Sensing.

A new ‘Off–On’ system designed and synthesised by functionalisation of a naphthalene diimide (NDI) core with dimethylamine produces 4,9‐bis(dimethylamino)‐2,7‐dioctylbenzo[lmn][3,8]‐phenanthroline‐1,3,6,8‐(2H,7H)‐tetraone, abbreviated as DDPT (1). DDPT 1 was synthesised using a simple strategy, namely aromatic nucleophilic substitution using Br2‐NDI with dimethylamine at 110 °C. DDPT was characterized by 1H and 13C NMR spectroscopy, ESI mass spectrometry and elemental analysis. DDPT 1 was then used for optical studies through protonation of its dimethylamine core with trifluoroacetic acid (TFA), blue‐shifting the absorption band from 600 nm to 545 nm in solution. Interestingly, the fluorescence of DDPT 1 is weak in solution with a quantum yield Φ=0.09, which is significantly enhanced to Φ=0.78 upon addition of TFA. The limit of detection (LOD) was determined to 2.77 nm. Furthermore, DDPT 1 can be used for naked eyed detection not only under UV light (365 nm) but also using visible light, as clear changes can be clearly seen upon addition of TFA. The binding constant of DDPT was calculated to 2.1×10−3 m −1. Importantly, DDPT 1 showed reversible switching by alternative addition of acid (TFA) and base (triethylamine) without loss of activity. Immobilised on paper, DDPT 1 can be used for strip‐test sensing in which the colour changes from blue to reddish when expose to TFA vapours and reverse in the presence of triethylamine vapours.

Comparative analysis of the chemical constituents and in vitro antioxidant activities of different aqueous extracts of Cistanche phelypaea (L.) Cout. from Algeria

• Different aqueous extracts were prepared from Cistanche phelypaea roots. • Decoction presented the highest total phenolic content. • Identical qualitative chromatographic patterns were observed for all extracts. • Quantitative variations were highlighted in some of the identified compounds. • Cold maceration gave the extract with the weakest ferric reducing power activity. Cistanches herba are well-known for their nutritional and therapeutic effects, but only few reports are available about the species Cistanche phelypaea (L.) Cout. and studies of aqueous extracts are scarce. This study aimed to elucidate the impact of aqueous extraction methods including decoction, infusion and cold maceration from C. phelypaea roots on phytochemical composition and in vitro antioxidant activities of the extracts. In order to accomplish this, determinations of total phenolic and flavonoid contents, liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS and LC/ESI-MS/MS) analyses and in vitro antioxidant activity studies were carried out. All extracts had significant levels of total phenolic content, but the decoction possessed the highest concentration and no significant difference was observed between infusion and cold maceration. Concerning flavonoids, decoction and infusion possessed the highest concentrations. Data obtained from LC/ESI-MS and LC/ESI-MS/MS analyses showed similar qualitative profiles for all aqueous extracts with 14 characteristic chromatographic peaks in negative mode and 6 in positive mode, which allowed the tentative identification of syringin, 14 phenylethanoid glycosides and 5 iridoids, including 5 pairs of isomers. However, significant variations were recorded for the relative abundance of some compounds depending on the method that was employed. Hot extraction procedures, decoction and/or infusion were more efficient in extracting acteoside, isoacteoside and two molecules corresponding to isomers of 2ʹ-acetylacteoside/tubuloside B, and it seems that a longer time of heating-extraction was required for an improved extraction of isoacteoside, and one of the two isomers of 2ʹ-acetylacteoside/tubuloside B, as decoction gave a significant higher amount of these compounds. However, 8-epiloganic acid and cistanoside F, with their respective isomers, and syringin were more extractable by the cold maceration process. All extracts had similar antioxidant properties in scavenging DPPH radical and total antioxidant activity assays, with the exception of the ferric-reducing power activity assay, in which cold maceration exhibited a significantly less potent activity. Aqueous extracts of C. phelypaea roots present an interesting antioxidant potential which is related to the synergistic effects of several antioxidant compounds.