High-resolution Electrospray Ionization Mass Research Articles

Antiglioma Natural Products from the Marine-Associated Fungus Penicillium sp. ZZ1750

Marine-derived Penicillium fungi are one of the most important sources for the discovery of new bioactive natural products. This study characterized the isolation, structures, and antiglioma activities of twelve compounds, including three novel ones—penipyridinone B (1), 11S-(−)-penilloid A (2), and 11R,14E-(+)-penilloid A (3)—from the marine fungus Penicillium sp. ZZ1750. The structures of the novel compounds were determined via extensive nuclear magnetic resonance (NMR) spectroscopic analyses, high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, Mosher’s method, optical rotation (OR) calculations, and electronic circular dichroism (ECD) calculations. Penipyridinone B represents the first example of its structural type and showed potent antiglioma activity, with IC50 values of 2.45 μM for U87MG cells and 11.40 μM for U251 cells. The known compounds of questiomycin A (9) and xanthocillin X (10) also showed antiproliferative activity against both U87MG and U251 cells, with IC50 values of 13.65 μM to 22.56 μM. The antiglioma activity of questiomycin A and xanthocillin X may be related to the promotion of reactive oxygen species (ROS) production, the reduction of mitochondrial membrane potential (MMP), and the enhancement of caspase-3 enzyme activity.

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.

Identification of Exhaled Metabolites in Children with Cystic Fibrosis.

The early detection of inflammation and infection is important to prevent irreversible lung damage in cystic fibrosis. Novel and non-invasive monitoring tools would be of high benefit for the quality of life of patients. Our group previously detected over 100 exhaled mass-to-charge (m/z) features, using on-line secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS), which distinguish children with cystic fibrosis from healthy controls. The aim of this study was to annotate as many m/z features as possible with putative chemical structures. Compound identification was performed by applying a rigorous workflow, which included the analysis of on-line MS2 spectra and a literature comparison. A total of 49 discriminatory exhaled compounds were putatively identified. A group of compounds including glycolic acid, glyceric acid and xanthine were elevated in the cystic fibrosis group. A large group of acylcarnitines and aldehydes were found to be decreased in cystic fibrosis. The proposed compound identification workflow was used to identify signatures of volatile organic compounds that discriminate children with cystic fibrosis from healthy controls, which is the first step for future non-invasive and personalized applications.

A New 1,3-Benzodioxole Compound from Hypecoum erectum and Its Antioxidant Activity.

The purpose of this study was to identify the chemical components in aerial parts of Hypecoum erectum. A new 1,3-benzodioxole derivative, identified as Hypecoumic acid (1), was isolated, together with the three known compounds: protopine (2), coptisine (3), and cryptopine (4). Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectra (HR-ESI-MS), as well as comparison with those reported in the literature. Meanwhile, the in vitro antioxidative activity of all compounds was determined using a DPPH-scavenging assay, and compound 1 (IC50 = 86.3 ± 0.2 μM) was shown to have moderate antioxidative activity.

A new meroterpenoid and a new polyketide from Penicillium expansum GY618 Fungus

Two new compounds, including one meroterpenoid ( 1 ) and a polyketide derivative ( 2 ), along with six compounds ( 3 − 8 ), were isolated from the rice solid fermentation of Penicillium expansum GY618. The structures of these new compounds were elucidated through interpretations of spectroscopic data and highresolution electrospray ionization mass spectrometry. The absolute configurations of all new compounds were unambiguously established through the optical rotation or calculation of the ECD spectrum. All isolated compounds were evaluated for their antibacterial and antitumor activities. Compound 6 exhibited weak antitumor activity. • One new meroterpenoid and a new polyketide derivative were isolated. • The absolute configuration of all new compounds was unambiguously established. • Compound 6 showed weak antitumor activity.

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.

Validating Discriminative Signatures for Obstructive Sleep Apnea in Exhaled Breath.

Rapid and reliable tools for the diagnosis and monitoring of obstructive sleep apnea (OSA) are currently lacking. Prior studies using a chemical analysis of exhaled breath have suggested the existence of an OSA-specific metabolic signature. Here, we validated this diagnostic approach and the proposed marker compounds, as well as their potential to reliably diagnose OSA. In this cross-sectional observational study, exhaled breath was analyzed using secondary electrospray ionization high-resolution mass spectrometry. The study cohort included untreated OSA patients, OSA patients treated with continuous positive airway pressure and healthy subjects. The robustness of previously reported OSA markers was validated based on detectability, significant differences between groups (Mann–Whitney U test) and classification performance. The breath analysis of 118 participants resulted in 42 previously reported markers that could be confirmed in this independent validation cohort. Nine markers were significantly increased in untreated OSA compared to treated OSA, with a subset of them being consistent with a previous validation study. An OSA prediction based on the confirmed OSA signature performed with an AUC of 0.80 (accuracy 77%, sensitivity 73% and specificity 80%). As several breath markers were clearly found to be repeatable and robust in this independent validation study, these results underscore the clinical potential of breath analysis for OSA diagnostics and monitoring.

Cytotoxic ent-Kaurane Diterpenoids from Rabdosia Rubescens.

One new (1) and 11 reported ent-kaurane diterpenoids (2-12) were received from the ethanol extract of the air-dried aerial parts of Rabdosia rubescens collected in Jiyuan. Their structures were determined in accordance with high resolution electrospray ionization mass spectroscopy, one dimensional (1D) and two-dimensional (2D) NMR spectroscopy and the data published in the literature. The cytotoxic activity of these isolated compounds was assessed against SMMC-7721, A-549, H-1299 and SW-480 cancer cell lines. Compounds 2-6 revealed significant cytotoxic activity on lung cancer cell lines A549 with IC50 values from 6.2 to 28.1 μM. Analysis of structure-activity relationship of these tested compounds indicated the carbonyl at C-15 and hydroxy at C-1 together could be crucial groups for inhibiting lung cancer cell lines A549 proliferation.

Bistrochelides H−L: Biscembranoids from the south China sea soft coral Sarcophyton serenei

Five undescribed biscembranoids, bistrochelides H−L, along with four known biscembranoids, glaucumolides A−B and bistrochelides A−B, were isolated from the soft coral Sarcophyton serenei collected off the Xisha Island in the South China Sea. The structures of these compounds were elucidated by HRESIMS (high-resolution electrospray ionization mass spectroscopy) spectrometry, NMR (nuclear magnetic resonance) spectroscopy, X-ray diffraction analysis, electronic circular dichroism (ECD), and the comparison of their spectroscopic data with those reported in the literature. In bioassay, some compounds showed a strong inhibitory effect on osteoclast precursor cells at the concentration of 10 μM. Additionally, all compounds exhibited weakly antimicrobial activity against Vibrio harveyi.

Acyltransferase Domain Swapping for the Production of Tenvermectin B Metabolites in Genetically Engineered Strain Streptomyces avermitilis HU02.

Tenvermectins A and B (TVMs A and B) are hybrid natural compounds of avermectins and milbemycins with enhanced insecticidal activity. Aiming at obtaining a strain for the production of the higher activity metabolite-TVM-B as a major constituent, a recombinant strain Streptomyces avermitilis HU02 was constructed by a domain swapping strategy in which milA1-AT0 gene in S. avermitilis MHJ1011 was replaced by eryA1-AT0 gene from Saccharopolyspora erythraea ATCC 40137. Chemical investigation on the culture of S. avermitilis HU02 led to the isolation of a large amount of TVM-B and trace amounts of five new TVM-B analogues. The structures of new metabolites were elucidated by extensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The bioassay test indicated that five new TVM-B analogues exhibited potent insecticidal activity against Tetranychus cinnabarinus and Bursaphelenchus xylophilus. This study provided a feasible route to the low-cost production of TVM-B and enriched the structural diversity of TVM-B metabolites.

The spectroscopic and computational study of anthracene based chemosensor - Ag+ interactions

Here in, we demonstrate a selective detection of Ag+ ion by the anthracene-based schiff base sensor AMC. The recognition event among sensor AMC and Ag+ ion was investigated by enhanced absorption band, red-shifted quenched emission spectra, electrochemical studies and DFT computational studies. The presence of Ag+ ion to solution of AMC quenched almost 50 % emission intensity of the ligand band. Data from high-resolution electrospray ionization mass spectrometry (ESI-HRMS), Ag+ titrations, and Job's plot studies all show that Ag+ binds to AMC in a 1:1 stoichiometric ratio.The quantitative parameters of sensor for silver ion are determined as the limit of detection (LOD) 5.95 × 10-7 M, and limit of quantitation (LOQ) 1.98 × 10-8 M in the linear range 3.48–20.31 × 10-6 M with good association affinity of 5.030 × 103 M−1. LMCT phenomenon from insilico studies, is in good agreement with the results obtained from other performed spectroscopic techniques. In addition, this sensor AMC was also successfully applied to real water samples for the identification and measurement of Ag+ ions.

Metabolomic changes in lactating multiparous naturally MAP-infected Holstein-Friesian dairy cows suggest changes in mitochondrial energy pathways

Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of Johne's Disease, a chronic intestinal infection of ruminants. Infected cows begin shedding MAP within the asymptomatic, subclinical stage of infection before clinical signs, such as weight loss, diarrhoea and reduced milk yields develop within the clinical stages of disease. Herein, we examine the milk metabolomic profiles of naturally MAP-infected Holstein-Friesian cows. The study used biobanked milk samples which were collected 73.4 ± 3.79 (early lactation) and 143 ± 3.79 (mean ± SE) (mid-lactation) days post-calving from 5 MAP-infected and 5 control multiparous cows. The milk metabolome was assessed using flow infusion electrospray high-resolution mass spectrometry (FIE-HRMS) for sensitive, non-targeted metabolite fingerprinting. Metabolite fingerprinting assessments using partial least squares discriminate analyses (PLS-DA) indicated that lactation stage was a larger source of variation than MAP status. Examining each lactation stage separately for changes associated to MAP-infection status identified 45 metabolites, 33 in early lactation and 12 in mid-lactation, but only 6 metabolites were targeted in both stages of lactation. Pathway enrichment analysis suggested that MAP affected the malate-aspartate shuffle during early lactation. Pearson's correlation analysis indicated relationships between milk lactose concentrations in mid-lactation and 6 metabolites that were tentatively linked to MAP-infection status. The targeted metabolites were suggestive of wider changes in the bioenergetic metabolism that appear to be an acceleration of the effects of progressing lactation in healthy cows. Additionally, milk lactose concentrations suggest that MAP reduces the availability of lactose derivatives.

Facile Access to 2-Selenoxo-1,2,3,4-tetrahydro-4-quinazolinone Scaffolds and Corresponding Diselenides via Cyclization between Methyl Anthranilate and Isoselenocyanates: Synthesis and Structural Features.

A practical method for the synthesis of 2-selenoxo-1,2,3,4-tetrahydro-4-quinazolinone was reported. The latter compounds were found to undergo facile oxidation with H2O2 into corresponding diselenides. Novel organoselenium derivatives were characterized by the 1H, 77Se, and 13C NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, IR, elemental analyses (C, H, N), and X-ray diffraction analysis for several of them. Novel heterocycles exhibited multiple remarkable chalcogen bonding (ChB) interactions in the solid state, which were studied theoretically.

Terpenoids from the Seeds of Toona sinensis and Their Ability to Attenuate High Glucose-Induced Oxidative Stress and Inflammation in Rat Glomerular Mesangial Cells.

Toona sinensis (A. Juss.) Roem is an edible medicinal plant that belongs to the genus Toona within the Meliaceae family. It has been confirmed to display a wide variety of biological activities. During our continuous search for active constituents from the seeds of T. sinensis, two new acyclic diterpenoids (1–2), together with five known limonoid-type triterpenoids (3–7), five known apotirucallane-type triterpenoids (8–12), and three known cycloartane-type triterpenoids (13–15), were isolated and characterized. Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectra (HR-ESI-MS), and electronic circular dichroism (ECD), as well as the comparison with those reported in the literature. We compared these findings to those reported in the literature. Compounds 5, 8, and 13–14 were isolated from the genus Toona, and compounds 11 and 15 were obtained from T. sinensis for the first time. The antidiabetic nephropathy effects of isolated compounds against high glucose-induced oxidative stress and inflammation in rat glomerular mesangial cells (GMCs) were assessed in vitro. The results showed that new compounds 1 and 2 could significantly increase the levels of Nrf-2/HO-1 and reduce the levels of NF-κB, TNF-α, and IL-6 at concentrations of 30 μM. These results suggest that compounds 1 and 2 might prevent the occurrence and development of diabetic nephropathy (DN) and facilitate the research and development of new antioxidant and anti-inflammatory drugs suitable for the prevention and treatment of DN.

Rapid detection of Staphylococcus aureus and Streptococcus pneumoniae by real-time analysis of volatile metabolites

SummaryEarly detection of pathogenic bacteria is needed for rapid diagnostics allowing adequate and timely treatment of infections. In this study, we show that secondary electrospray ionization–high resolution mass spectrometry (SESI-HRMS) can be used as a diagnostic tool for rapid detection of bacterial infections as a supportive system for current state-of-the-art diagnostics. Volatile organic compounds (VOCs) produced by growing S. aureus or S. pneumoniae cultures on blood agar plates were detected within minutes and allowed for the distinction of these two bacteria on a species and even strain level within hours. Furthermore, we obtained a fingerprint of clinical patient samples within minutes of measurement and predominantly observed a separation of samples containing live bacteria compared to samples with no bacterial growth. Further development of this technique may reduce the time required for microbiological diagnosis and should help to improve patient’s tailored treatment.

Antitumor Potential of Withanolide Glycosides from Ashwagandha (Withania somnifera) on Apoptosis of Human Hepatocellular Carcinoma Cells and Tube Formation in Human Umbilical Vein Endothelial Cells.

Hepatocellular carcinoma (HCC) is the fastest-growing tumor capable of spreading to other organs via blood vessels formed by endothelial cells. Apoptosis and angiogenesis-targeting therapies are attractive for cancer treatment. In this study, we aimed to study the in vitro cytotoxicity of Withania somnifera against human HCC (HepG2) cells, identify potential antitumoral withanolide glycosides from the active fraction, and elucidate cytotoxic molecular mechanisms of identified bioactive compounds. W. somnifera (Solanaceae), well-known as ‘ashwagandha’, is an Ayurvedic medicinal plant used to promote health and longevity, and the MeOH extract of W. somnifera root exhibited cytotoxicity against HepG2 cells during initial screening. Bioactivity-guided fractionation of the MeOH extract and subsequent phytochemical investigation of the active n-BuOH-soluble fraction resulted in the isolation of five withanolide glycosides (1–5), including one new metabolite, withanoside XIII (1), aided by liquid chromatography–mass spectrometry-based analysis. The new compound structure was determined by 1D and 2D nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, electronic circular dichroism, and enzymatic hydrolysis. In addition, withanoside XIIIa (1a) was identified as the new aglycone (1a) of 1. Isolated withanolide glycosides 1–5 and 1a were cytotoxic toward HepG2 cells; withagenin A diglucoside (WAD) (3) exhibited the most potent cytotoxicity against HepG2 cells, with cell viability less than 50% at 100 μM. WAD cytotoxicity was mediated by both extrinsic and intrinsic apoptosis pathways. Treatment with WAD increased protein expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Bcl-2-associated X protein (Bax), and cleaved poly(ADP-ribose) polymerase (cleaved PARP) but decreased expression levels of B-cell lymphoma 2 (Bcl-2). Moreover, WAD inhibited tubular structure formation in human umbilical vein endothelial cells (HUVECs) by inhibiting the protein expression of vascular endothelial growth factor receptor 2 and its downstream pathways, including extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). These effects were also enhanced by co-treatment with ERK and PI3K inhibitors. Overall, these results indicate that WAD (3) induced HepG2 apoptosis and inhibited HUVEC tube formation, suggesting its potential application in treating liver cancers.

Analgesic monoterpene indole alkaloids from Gelsemium elegans stems

ObjectiveThe aim of this study is to search for potent analgesics from the stems of Gelsemium elegans. MethodsAlkaloids were isolated from the samples of G. elegans and purified using column chromatograph and High-Performance Liquid Chromatography. The chemical structures of the isolated alkaloids were determined using extensive high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data analyses, 13C NMR DP4+ analysis and electronic circular dichroism (ECD) calculations, and Rh2(OCOCF3)4-induced ECD data analysis. The analgesic activities of all the isolates were analyzed using an acetic acid-induced writhing test in mice. ResultsTwo new monoterpene indole alkaloids, elegansine A (1) and 14-hydroxysempervirine (2), and seven known monoterpene indole alkaloids were isolated from the stems of G. elegans. Elegansine A (1) represents the first example of sarpagine-type alkaloids with a Δ15(20) double bond. All the alkaloids (1–9) showed potential analgesic activities. Three alkaloids, namely 14-hydroxysempervirine (2), 14β,20α-dihydroxydihydrorankinidine (4), and 14-hydroxygelsenicine (6), exhibited significant analgesic activities in the acetic acid-induced writhing test in mice at a dose of 5.0 mg/kg with the writhing inhibition rates of 69.5%, 69.2%, and 72.7%, respectively. ConclusionThese results enlarged the diversity of monoterpene indole alkaloids and also provided a new basis to develop novel potent analgesics.

Antitobacco Mosaic Virus Activity of a New Eremophilane Glucoside From the Leaves of Nicotiana tabacum L

A new eremophilane-type sesquiterpene glucoside, 13-hydroxycapsidiol 3- O- β-D-glucoside (1), was isolated from the leaves of Nicotiana tabacum L. The structure of this new metabolite was determined by one-dimensional (1D) and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and comparison with values reported in the literature. Compound 1 was the second glycosylated eremophilane sesquiterpenoid isolated from plants of the Solanaceae family and exhibited a more potent anti-tobacco mosaic virus (anti-TMV) activity, with an inhibition rate of 39.4% at 20 μM, than the positive control ningnanmycin (34.8%).

Cytotoxic Biflavonoids from Selaginella braunii

A new biflavonoid, (2″ S)-8″-C-methyl-2″,3″-dihydrorobustaflavone-4′-methyl ether (1) and 5 known robustaflavones (2-6) were isolated from the 70% EtOH extract of Selaginella braunii for the first time. The structures of 1 and the known compounds were identified by performing a comprehensive analysis of spectroscopic data including ultraviolet-visible, high-resolution electrospray ionization mass spectrometry, 1-dimensional and 2-dimensional nuclear magnetic resonance, and circular dichroism spectra. Compounds 1-6 were determined for cytotoxic activity against 3 human cancer cell lines (SMMC-7721, MCF-7, and A549). Compound 1 exerted apparent antiproliferative effects on SMMC-7721, MCF-7, and A549 cells, with IC50 values of 18.6, 16.7, and 25.5 μM, respectively.

Novel phenylacetate derivatives isolated from the fungus Penicillium canescens

Two undescribed phenylacetate derivatives (compounds 1 and 2) with a known analog were isolated from a soil-derived fungus Penicillium canescens through the “one strain-many compounds” method. The new structures were assigned using extensive 1D and 2D NMR spectra, high-resolution electrospray ionization mass spectrometry, and the comparison of coupling cleavages of known compounds, which are two pairs of racemic mixtures of aromatic polyketides with a terminal butan-2,3-diol group. In the bioassay, the biological screening signifies no cytotoxic activities against several human cancer cell lines (HL-60, A549, SMMC-7721, MCF-7, and SW480) at a concentration of 40.0 µM.