High-resolution Electrospray Ionization Mass Spectrometry Research Articles

Activity of an oleanane-type tritrepenoid saponin from A. glycyphyllos on human recombinant MAO enzymes

For centuries, plants have been a leading point in the identification of potential therapeutic agents. Monoamine oxidase inhibition is a key mechanism in the treatment of various neurological and psychiatric diseases. Some triterpenoid saponins are reported to inhibit this enzyme. An extract from the aerial parts of Astragalus glycyphyllos was purified and separated by chromatographic techniques, which led to the isolation of one triterpene saponin. Its structure was analysed by ultra-high-performance liquid chromatography coupled with high-resolution electrospray ionisation mass spectrometry. The compound was subjected to a pharmacological study where human recombinant monoamine oxidase enzymes type A and B (hMAOA and hMAOB) were used. On the activity of hMAOA, the saponin had no effect, but on hMAOB, it exhibited statistically significant inhibition in comparison to the control, Selegiline. The compound could have potential in other models, so further investigations are required.

New indole derivatives from endophytic fungus Colletotruchum sp. HK-08 originated from leaves of Nerium indicum

ObjectiveTo study secondary metabolites from endophytic fungus Colletotruchum sp. HK-08 originated from the leaves of Nerium indicum. MethodsThe compounds were isolated by various column chromatographic techniques, and their structures were elucidated by spectroscopic techniques [high resolution electrospray ionization mass spectroscopy (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance spectroscopy (NMR)], as well as comparison with literature data. The Ellman method was used to determine the acetylcholinesterase (AChE) inhibitory activity. ResultsFour indole derivatives were identified from Colletotruchum sp. HK-08, including 6′-hydroxymonaspiloindole (1), 2-(2-oxoindolin-3-yl)ethyl 2-(4-hydroxyphenyl) acetate (2), 2-(2-oxoindolin-3-yl)ethyl 2-(2-hydroxyphenyl)acetate (3), and monaspiloindole (4). Compound 4 presented weak AChE inhibitory activity with IC50 value of (69.30 ± 6.27) μmol/L [tacrine as the positive control, with IC50 value of (0.61 ± 0.07) μmol/L]. ConclusionCompounds 1–3 were new compounds, and compound 4 had weak AChE inhibitory activity.

Pharmacokinetic study of osilodrostat and identification of mono-hydroxylated metabolite in equine plasma for the purpose of doping control.

Osilodrostat is an inhibitor of 11-beta-hydroxylase (CYP11B) and is used for the treatment of Cushing's disease but also categorized as an anabolic agent. The use of osilodrostat is prohibited in horseracing and equestrian sports. To the best of our knowledge, this is the first metabolic study of osilodrostat in equine plasma. Potential metabolites of osilodrostat were identified by differential analysis using data acquired from pre- and post-administration plasma samples after protein precipitation with liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI-HRMS). [Correction added on 27 January 2023, after first online publication: In the preceding sentence, "C-HRMS" was changed to "LC/ESI-HRMS" in this version.] For quantification of osilodrostat, a strong cation exchange solid-phase extraction was employed, and the extracts were analyzed using LC/ESI-triple quadrupole tandem mass spectrometry (LC/ESI-QqQ-MS/MS)to establish its elimination profile. Such extracts were further analyzed using LC/ESI-HRMS to investigate the detectability of osilodrostat and its identified mono-hydroxylated metabolite over a 2-week sampling period. Mono-hydroxylated osilodrostat was identified based on the differential analysis and mass spectrometric interpretations, and it was found to be the most abundant metabolite in plasma. Elimination profile of osilodrostat in plasma was successfully established over the 24-h post-administration period. Both osilodrostat and its mono-hydroxylated metabolite were detected up to the last sampling point at 2weeks using HRMS, and osilodrostat could be confirmed up to 8-day post-administration with its reference material using HRMS as well. For doping control, screening of both the parent drug osilodrostat and its mono-hydroxylated metabolite in equine plasma would be recommended due to their extended detection windows of up to 2weeks. Given the availability of reference material for potential confirmation in forensic samples, osilodrostat is considered the most appropriate monitoring target.

Bioprospection of Tenellins Produced by the Entomopathogenic Fungus Beauveria neobassiana.

Fungi are known as prolific producers of bioactive secondary metabolites with applications across various fields, including infectious diseases, as well as in biological control. However, some of the well-known species are still underexplored. Our current study evaluated the production of secondary metabolites by the entomopathogenic fungus Beauveria neobassiana from Thailand. The fermentation of this fungus in a liquid medium, followed by preparative high-performance liquid chromatography (HPLC) purification, resulted in the isolation of a new tenellin congener, namely pretenellin C (1), together with five known derivatives (2-6). Their chemical structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy in combination with high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). We evaluated the antimicrobial and cytotoxic activities from all isolated compounds, as well as their inhibitory properties on biofilm formation by Staphylococcus aureus. Generally, tenellins displayed varying antibiofilm and cytotoxic effects, allowing us to propose preliminary structure-activity relationships (SARs). Among the tested compounds, prototenellin D (2) exhibited the most prominent antibiofilm activity, while its 2-pyridone congener, tenellin (4), demonstrated potent cytotoxic activity against all tested cell lines. Given the fact that the biological activities of the tenellins have so far been neglected in the past, our study could provide a good starting point to establish more concise structure-activity relationships in the near future.

Design, synthesis, antifungal activity and molecular docking of novel pyrazole-4-carboxamides containing tertiary alcohol and difluoromethyl moiety as potential succinate dehydrogenase inhibitors.

Resistance problems with the long-term and frequent use of existing fungicides, and the lack of structure diversity of traditional pyrazole-4-carboxamide succinate dehydrogenase inhibitors, it is highly required to design and develop new fungicides to address the resistance issue. Different from previous pyrazole-4-carboxamide succinate dehydrogenase inhibitors by breaking the norm of difluoromethyl at the C-3 position of pyrazole and introducing a tertiary alcohol group at the C-3 position, 27 novel pyrazole-4-carboxamide derivatives were designed, synthesized and characterized by proton (1 H) nuclear magnetic resonance (NMR), carbon-13 (13 C) NMR, fluorine-19 (19 F) NMR and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The crystal structures of compounds A14 and C5 were analyzed by single crystal X-ray diffraction. Their in vitro antifungal activities were evaluated against phytopathogen Fusarium graminearum, Botrytis cinerea, Phytophthora capsica, Sclerotinia sclerotiorum, Thanatephorus cucumeris. The results displayed that most of them exhibited significant antifungal activities against S. sclerotiorum at 50 mg/L, the half maximal effective concentration (EC50 ) data of A8 and A14 were 3.96 and 2.52 mg/L, respectively. Their in vivo antifungal activities were evaluated against Pseudoperonospora cubensis, Puccinia sorghi Schw, Colletotrichum gloeosporioides, F. graminearum, Erysiphe graminis, Thanatephorus cucumeris, the control efficacies of A6, B3, C3, and C6 against E. graminis reached 100% at a concentration of 400 mg/L. The molecular docking results showed that the binding mode of the target compounds containing tertiary alcohols were similar to that of fluxapyroxad in succinate dehydrogenase. In addition, tertiary alcohols were involved in the formation of hydrogen bonds. The excellent in vitro and in vivo inhibitory activities of novel pyrazole-4-carboxamide derivatives against succinate dehydrogenase were reported for the first time, and they could be used as the potential lead compounds. © 2023 Society of Chemical Industry.

Cobalt pyridyl complexes against drug-resistant bacteria: Synthesis, characterization, antibacterial properties, mode of action, and molecular docking studies

This study describes the synthesis and characterization of four cobalt complexes using diverse physicochemical techniques. Notably, the co-grinding method was predominantly employed, resulting in higher yields and increased purity of the products. Thermal studies provided insights into the stability of the cobalt complexes, with dichoro-bis-4-((4-nitrophenoxy)methyl)pyridine cobalt(II) (CoL4) demonstrating the highest stability based on transformations and high melting points. High resolution electrospray ionization mass spectrometry (HRESI-MS) analysis further confirmed the successful synthesis of the cobalt complexes, reinforcing the characterization results. The dichloro-bis(pyridin-4ylmethyl-4aminobenzoate) cobalt (II) (CoL3) exhibited a cis tetrahedral structure with a high-symmetry monoclinic crystal system and a primitive lattice centering of an I2/a space group. The cobalt complexes displayed enhanced activity against Gram-negative bacteria, particularly Klebsiella pneumoniae, with some exhibiting potent bacteriostatic effects against Multidrug resistant K. pneumoniae (MDR-K. pneumoniae). Additionally, dichoro-bis-(4-[(pyridin-4-yl)methoxy] aniline) cobalt(II) (CoL2) and CoL3 were found to disrupt the folate biosynthesis of K. pneumoniae and Methicillin resistant Staphylococcus aureus (MRSA), respectively. Moreover, 4-chloromethylpyridinium tetrachlorocobaltate (II) (Co4PY-H), dichloro-bis-4-picolyl cobalt (II) (Co4PY), CoL2, and CoL3 showed significant disruption of the cell membrane integrity of K. pneumoniae, with CoL3 also affecting MRSA's cell membrane. Lastly, molecular docking calculations provided compelling evidence supporting the experimental modes of action of these active complexes.

Polyhydroxy Sterols Isolated From Ganoderma sinense Spores and Their Cytotoxic Activities

Background: The fruiting body of Ganoderma sinense Zhao, Xu et Zhang iscertified as an authoritative medical material in the Chinese Pharmacopoeia 2020 edition and has been used as a crude drug for a long time. G sinense spores are crucial part of the fruiting body of G sinense and exhibited antitumor and immune-enhancing activities according to our previous reports. However, there were few studies about the chemical composition of G sinense spores. This study was aimed at the structure determination and antitumor effect of the sterols isolated from G sinense spores. Methods: Modern chromatographic methods were applied to isolate compounds from the ruptured spores of G sinense. Their chemical structures were elucidated by analyses of one-dimensional and two-dimensional 1H nuclear magnetic resonance, and high-resolution electrospray ionization mass spectrometry data. The cytotoxicities of the isolated compounds against 3 tumor cell lines, human non-small cell lung cancer A549 and 95D cells, and human hepatocellular carcinoma HepG2 cells were measured by Cell Counting Kit-8. Results: A novel ergosterol derivative, (22 E,24 R)-3β,5β,6α,7α,14β-pentahydroxyergosta-8,22-dien-15-one (1), and 5 known sterols, (22 E,24 R)-3β,5α,9α,14β-tetrahydroxyergosta-7,22-dien-6-one (2), (22 E,24 R)-ergosta-7,9(11),22-triene-3β,5α,6β-triol (3), (22 E,24 R)-ergosta-7,9(11),22-triene-3β,5α,6β,14α-tetrol (4), β-daucosterine (5), and (22 E,24 R)-ergosta-7,22-diene-3β,5α,6β,9α-tetrol (6), were obtained from the ruptured spores of G sinense. Compound 1 exhibited cytotoxicity against A549 cells and HepG-2 cells with IC50 values of 65.12 ± 4.76 and 97.34 ± 6.36 μM, respectively. Compounds 1, 2, and 4 were obtained from G sinense for the first time. Conclusion: This paper is a continuation of an investigation of the chemical ingredients from G sinense spores and their antitumor effect. Only compound 1 showed weak cytotoxicities against A549 cells and HepG-2 cells.

Evolution of Polynuclear Gold(I) Sulfido Complexes from Clusters and Cages to Macrocycles.

Two unprecedented tetratriacontanuclear and tetraicosanuclear gold(I) sulfido clusters (denoted as Au34-LMe and Au24-LCbz) with different temperature-induced stimulus-responsive behavior and emission property have been constructed by taking advantage of the judiciously designed bidentate phosphine ligand. Au34-LMe represents the highest nuclearity of the gold(I) sulfido cluster with more than a thousand atoms in the molecule. Octagonal macrocycles based on metal-cluster nodes have been assembled for the first time. The self-assembly and temperature-induced stimulus-responsive processes were monitored by 1H and 31P{1H} NMR spectroscopy, and the identities of the discrete gold(I) complexes were established by single-crystal structural analysis and high-resolution electrospray ionization mass spectrometry data. The steric effects exerted by the substituents on the V-shaped 1,3-bis(diphenylphosphino)benzene ligand have been shown to govern the self-assembly from the 1D cluster and 3D cage to 2D macrocycles. This work not only offers a new strategy to construct and regulate the structure of 2D macrocyclic gold(I) sulfido complexes but also lays the foundation for the future precise design and controlled construction of higher polygonal and cluster-node macrocycles.

Synthesis, characterization, molecular docking, and cytotoxicity study of ruthenium (II/III) polypyridyl complexes

A new polypyridyl ligand 4‐(4‐nitrophenoxy)‐N,N‐bis (pyridin‐2‐ylmethyl)aniline (L1) and its three ruthenium (II/III) complexes, [Ru (Cl)3L1] (C1), [Ru(L1)2]Cl (C2), and [RuCl (dpa)L1] (C3) where dpa = 2,2‐dipyridylamine, have been successfully synthesized and characterized using Fourier‐transform infrared spectroscopy (FTIR), elemental analysis, proton nuclear magnetic resonance (1H NMR), high‐resolution electrospray ionization mass spectrometry (HR‐ESI‐MS), thermal analysis (thermogravimetric analysis [TGA] and differential scanning calorimetry [DSC]), UV/Vis absorption, and magnetic susceptibility. The structures of the ligand and the complexes were optimized, and the structural characteristics were determined by density functional theory (DFT) using the B3LYP‐GD3/6‐311G++(d,p) method. Optimized FTIR vibrational frequencies and 1H NMR chemical shifts agreed well with the corresponding experimental FTIR and 1H NMR data. In vitro cytotoxicity of the ligand and the complexes were evaluated against the MCF‐7 breast cancer cell line. Ligand L1 was the most potent with an IC50 of 38.45 μM, followed by C2 with an IC50 of 45.23 μM. However, the ligand and the complexes showed low antiproliferative activity compared to cisplatin, which had an IC50 of 9.67 μM. To predict the reactivity trend of L1 and the complexes, frontier molecular orbital (FMO) analysis was performed. The FMO energy gap (Eg = ELUMO − EHOMO) for C2 was found to be 1.675 eV, which was the lowest among all the complexes or L1. In addition, molecular docking studies were carried out so as to predict the binding capacity of L1 and the complexes to estrogen receptor alpha (ER‐α). The results showed that C2 has the most negative binding energy score (−9.63 kcal/mol), which indicates more stable adducts with the key amino acid residues at the active sites of ER‐α. Furthermore, C2 displayed the lowest inhibition constant (Ki) of 0.09 μM compared to all the complexes or L1. These results are very promising and show that the novel complex C2 may help in the development of anticancer drugs.

Neosophoflavonoids A–C, A class of highly oxidized hybrid flavonoids from Sophora flavescens with antidiabetic effects

Three highly oxidized hybrid flavonoids neosophoflavonoids A–C (1, 2a, and 2b) were isolated from the roots of Sophora flavescens. Neosophoflavonoid A possesses a unique highly oxidized heptacyclic 6/6/6/6/6/6/5 system. Neosophoflavonoids B and C are isomers and share the same highly oxidized hexacyclic 6/6/6/6/6/6 systems. Their planar structures were elucidated from 1D/2D nuclear magnetic resonance (NMR), ultraviolet spectroscopy (UV), infrared spectroscopy (IR), and high resolution electrospray ionization mass spectroscopy (HRESIMS) data. Their absolute configurations were determined by thorough GIAO 13C NMR (DP4+) calculation protocol and electronic circular dichroism (ECD) calculation method. The plausible biosynthetic routes for the compounds were also proposed. All compounds exhibited significant protein tyrosine phosphatase-1B (PTP1B) inhibitory activity with half maximal inhibitory concentration (IC50) values 3.94 ± 0.01, 0.38 ± 0.13, and 0.70 ± 0.01 µmol/L, respectively. In addition, compared to a positive control fenofibrate (Feno) at 20 µmol/L, compounds 2a and 2b exhibited stronger inhibitory effects on lipid accumulation in the oleic acid (OA)-induced cell model at 5 and 10 µmol/L.

New ψ-Santonin Derivatives from Crossostephium chinense and Their Anti-Proliferative Activities against Leishmania major and Human Cancer Cells A549.

Previously, we reported two cytotoxic ψ-santonin-amino acid conjugates isolated from the EtOAc layer of Crossostephium chinense. However, a further phytochemical investigation seems to be required because of the few reports of similar derivatives. In this study, we targeted the 1-BuOH layer, which resulted in the isolation of seven new ψ-santonin derivatives (1-7) together with ten known compounds (8-17). The structures of 1-7 were elucidated based on spectroscopic methods, including 1D and 2D NMR experiments (1H, 13C, DEPT, COSY, HSQC, and HMBC), IR spectrum, and high-resolution electrospray ionization-mass spectrometry (HR-ESI-MS). The stereochemistry of new compounds was confirmed by NOESY and ECD calculations. All isolated compounds were evaluated by in vitro experiments for their anti-proliferative activities against Leishmania major, human lung cancer cell line A549, and Vero cells. As a result, most of the ψ-santonin derivatives, especially 1-5, showed significant cytotoxicity against L. major with a lower IC50 than the positive control we used (miltefosine).

Preservation of exhaled breath samples for analysis by off-line SESI-HRMS: proof-of-concept study

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of all m/z signals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.

Biooriented Synthesis of Ibuprofen-Clubbed Novel Bis-Schiff Base Derivatives as Potential Hits for Malignant Glioma: In Vitro Anticancer Activity and In Silico Approach.

This research work is based on the synthesis of bis-Schiff base derivatives of the commercially available ibuprofen drug in outstanding yields through multistep reactions. Structures of the synthesized compounds were confirmed by the help of modern spectroscopic techniques including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1H NMR, and 13C NMR. The synthesized compounds were evaluated for their anticancer activity using a normal human embryonic kidney HEK293 cell and U87-malignant glioma (ATCC-HTB-14) as a cancer cell line. All of the synthesized compounds among the series exhibited excellent to less antiproliferative activity having IC50 values ranging from 5.75 ± 0.43 to 150.45 ± 0.20 μM. Among them, compound 5e (IC50 = 5.75 ± 0.43 μM) was found as the most potent antiprolifarative agent, while 5f, 5b, 5a, 5n, 5r, 5s, 5g, 5q, 5i, and 5j exhibited good activity with IC50 values from 24.17 ± 0.46 to 43.71 ± 0.07 μM. These findings suggest that these cells (HEK293) are less cytotoxic to the activities of compounds and increase the cancer cell death in brain, while the lower cytotoxicity of the potent compounds in noncancerous cells suggests that these derivatives will provide promising treatment for patients suffering from brain cancer. The results of the docking study exposed a promising affinity of the active compounds toward casein kinase-2 enzyme, which shows green signal for cancer treatment.

Asperochones A and B, two antimicrobial aromatic polyketides from the endophytic fungus Aspergillus sp. MMC-2

Two novel fungal metabolites, asperochones A and B, were obtained from an Aspergillus sp. Their structures were determined by 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high resolution electrospray ionization mass spectroscopy (HRESIMS), and single-crystal X-ray diffraction analysis. Asperochone A possesses an intriguing skeleton bearing 5/6/6/6/7/5/5/5 octacyclic ring system, and asperochone B also exhibits an unusual carbon skeleton with five stereochiral centers. Their structures were proposed as heterotrimeric and heterodimeric products of aromatic polyketides. In addition, asperochone A exhibited a potential anti-tuberculosis effect since it showed a moderate potency against Mycobacterium smegmatis.

3‴-O-Foliamenthoyl-Rutin, a New Flavonoid Glycoside from the Roots of Nymphoides peltata.

Nymphoides peltata (Menyanthaceae) has been used as a medicinal herb in traditional medicines to treat conditions such as strangury, polyuria, swelling, and as a diuretic and antipyretic. In our ongoing research to discover novel structural and/or biological natural products in natural resources, five flavonoids, quercetin (1), quercitrin (2), isoquercetin (3), quercetin-3-O-vicianoside (4), and rutin (5), as well as a new flavonoid glycoside, 3‴-O-foliamenthoyl-rutin (6), were isolated from the MeOH extract of N. peltata roots. The chemical structure of the new compound (6) was determined by analyzing 1D and 2D NMR spectra and high-resolution (HR) electrospray ionization mass spectroscopy (ESIMS), along with a chemical reaction. The wound-healing activities of the isolated compounds (1-6) were evaluated using a HaCaT cell scratch test. Among the isolates, isoquercetin (3), quercetin-3-O-vicianoside (4), and 3‴-O-foliamenthoyl-rutin (6) promoted HaCaT cell migration over scratch wounds, with compound 4 being the most effective. Our findings provide experimental data supporting the potential of quercetin-3-O-vicianoside (4) as a wound-healing agent.

Apple extract protects against indomethacin-induced gastric ulcers in rats by suppressing oxidative stress – The implication of Nrf-2/HO-1 signaling pathway: In silico and in vivo studies

Gastric ulcers represent a worldwide health problem, characterized by erosions with different degrees in the gastrointestinal mucosa. In the current study, we explore the protective effects of the extract of apple seeds (Malus domestica, family: Rosaceae), regarded as environmental wastes, against indomethacin-induced gastric ulcers in rats. The chemical composition of the seeds extract was investigated through liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS). The metabolomics profiling resulted in identification of 17 compounds (1–17) of different chemical classes. The gene ontology analysis demonstrated that the total extract of M. domestica seeds possess an antiulcer activity through PI3K-Akt signaling pathway as the top identified signaling pathway. The present research work evidenced the reuse of apple seeds waste as an effective therapy to treat NSAIDs-induced gastric ulcer, attributed to its anti-inflammatory and antioxidant properties. It is important to note that the extract does not cause the undesirable effects of traditional antisecretory drugs.

Novel Diterpenoids Incorporating Rearranged Labdanes from the Chinese Liverwort Anastrophyllum joergensenii and Their Anti-inflammatory Activity.

Liverworts provide valuable ecological services to improve the sustainability of agriculture, encompassing soil health maintenance and natural pest management. Some liverworts have potential applications in medicine and as food additives. Twenty-two novel diterpenoids (anajoerins A-V), of which anajoerins B-G are rearranged labdanes featuring an unprecedented 6/5 fused ring system, were isolated from the Chinese liverwort Anastrophyllum joergensenii Schiffn. The absolute configurations of all compounds were identified based on high-resolution electrospray ionization mass spectroscopy data, NMR spectra, and ECD calculations. Plausible biogenetic pathways for unprecedented rearranged labdanes were proposed. Seven diterpenoids exhibited anti-inflammatory activity by reducing nitric oxide production in LPS-stimulated RAW264.7 murine macrophages in a dose-dependent manner with IC50s between 9.71 and 56.56 μM. All tested compounds showed no cytotoxicity at the tested concentrations. Western blot analyses of NF-κB p65 downregulation showed that anajoerin L could inhibit the NF-κB signaling pathway. Furthermore, anajoerin L also suppressed the secretion of the ConA-induced proinflammatory cytokines IFN-γ, TNF-α, and IL-6.

Unexpected Noremestrin with a Sulfur-Bearing 15-Membered Macrocyclic Lactone from Emericella sp. 1454.

Two previous unreported epipolythiodioxopiperazines of the emestrin family, namely, noremestrin A (1) and secoemestrin E (2), were successfully isolated from the fungal source Emericella sp. 1454. Employing comprehensive spectroscopic techniques, such as high-resolution electrospray ionization mass spectrometry, infrared, and nuclear magnetic resonance (NMR), along with NMR and electronic circular dichroism calculations, the chemical structures of compounds 1 and 2 were elucidated. Particularly noteworthy is the distinctive nature of noremestrin A, representing the inaugural instance of a noremestrin variant incorporating a sulfur-bearing 15-membered macrocyclic lactone moiety. Compounds 1 and 2 exhibited weak cytotoxic activities against the human chronic myelocytic leukemia cell lines MEG-01 and K562.

Aggregation-Induced Emission via the Restriction of the Intramolecular Vibration Mechanism of Pinacol Lanthanide Complexes.

Pinacol lanthanide complexes PyraLn (Ln = Dy and Tb) with the restriction of intramolecular vibration were obtained for the first time via an in situ solvothermal coordination-catalyzed tandem reaction using cheap and simple starting materials, thereby avoiding complex, time-consuming, and expensive conventional organic synthesis strategies. A high-resolution electrospray ionization mass spectrometry (HRESI-MS) analysis confirmed the stability of PyraLn in an organic solution. The formation process of PyraLn was monitored in detail using time-dependent HRESI-MS, which allowed for proposing a mechanism for the formation of pinacol complexes via in situ tandem reactions under one-pot coordination-catalyzed conditions. The PyraLn complexes constructed using a pinacol ligand with a butterfly configuration exhibited distinct aggregation-induced emission (AIE) behavior, with the αAIE value as high as 60.42 according to the AIE titration curve. In addition, the PyraLn complexes in the aggregated state exhibit a rapid photoresponse to various 3d metal ions with low detection limits. These findings provide fast, facile, and high-yield access to dynamic, smart lanthanide complex emissions with bright emission and facilitate the rational construction of molecular machines for artificial intelligence.

Chemical Constituents of the Deep-sea Gammarid Shrimp-Derived Fungus Penicillium citrinum XIA-16.

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0 μM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 μM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.