Comprehensive 2D Research Articles

Synthesis of the proposed structure of enhypyrazinone A, a rare marine-derived 3,5,6-tri-substituted pyrazinone secondary metabolite

Herein, we report the first total synthesis of enhypyrazinone A, a rare tri-substituted pyrazinone secondary metabolite that is isolated from the marine-derived myxobacterium Enhygromyxa sp. The key features of the synthesis involve a Horner-Wadsworth-Emmons (HWE) olefination to provide a crucial C5-substituted (E)-styryl group and the construction of a 3,5,6-tri-substituted pyrazinone skeleton from a highly functionalized dipeptide intermediate via pyridine-promoted cyclization and subsequent spontaneous aerobic oxidation. Although the 13C NMR spectra of the synthetic enhypyrazinone A slightly differed from those reported previously, the structure was confirmed by comprehensive 2D NMR analysis, including 1H–1H COSY, 1H–13C HSQC, and 1H–13C HMBC. Our concise and straightforward synthetic route provides the proposed structure of enhypyrazinone A with eight linear steps in 27.4% overall yield from commercially available Boc-Trp-OMe.

Paradoxical increase in left atrial strains early after Covid-19 infection, a result of comprehensive recovery phase four-chamber strains study.

Cardiac consequences of Covid-19 infection have been mentioned in various studies as a serious risk factor for in-hospital mortality. However, the existence of residual cardiac dysfunction after the acute phase is seldom investigated especially in people without a history of specific medical disease.One hundred health care workers with positive reverse transcription-polymerase chain reaction test underwent comprehensive 2D and 3D echocardiography six to eight weeks after infection. Patients were classified into Mild, Moderate, and Severe groups based on their clinical characteristics of covid-19 infection, and all echocardiographic parameters were compared between the three groups. Left ventricular (LV) stroke volume index was reduced in all groups compared to normal ranges and was more prominent in the severe group (P-value < 0.05). 3D-derived LV global longitudinal strain (GLS) was significantly lower in the severe group in comparison to the mild group (- 19.3 ± 1 Vs. - 22.2 ± 2, P-value < 0.001) and correlated with highly sensitive CRP level at the acute phase. Left atrial (LA) strains, including LA peak strain, LA contraction strain, and LA reservoir strain, were considerably higher and LA volume index was significantly lower in the clinically severe covid patients. Analysis based on the extent of lung involvement showed significantly increased 3D-derived right ventricular volumes in patients who experienced severe pneumonia despite normalized strains. Conclusion: subclinical LV dysfunction as reduced stroke volume index and GLS exists in the early recovery phase of normal individuals with severe course of covid-19. LA function indicated by LA strains paradoxically increases in severe covid-19 infection in this phase.

New antiprotozoal sesquiterpene derivatives from Dorema glabrum Fisch & C.A.Mey

Seven undescribed sesquiterpene derivatives, Azerins A-G (3–6, 8, 14 and 15), three known sesquiterpene phenols, kopetdaghin A (1), kopetdaghin B (2) and latisectin (7), together with five known sesquiterpene coumarins (9–13), were isolated from the roots of Dorema glabrum. The structures were elucidated by comprehensive 1D- and 2D-NMR spectral analysis as well as HR-ESI-MS. Compounds were assessed for their in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. Cytotoxic potentials of the compounds were also tested on L6 rat skeletal myoblasts. Azerin G (15) showed a potent preferential growth inhibitory activity against T. b. rhodesiense with IC50 value of 0.01 μM and selectivity index of 329. Compounds 1, 4, 7 and 8 were also found as the most active compounds with selective growth inhibitory effects toward P. falciparum with selectivity indices ranging from 11.6 to 16.7 (IC50: 1.8–24.6 μM).

Multiphase Polarization in Ion‐Intercalation Nanofilms: General Theory Including Various Surface Effects and Memory Applications

AbstractIon concentration polarization (CP, current‐induced concentration gradient adjacent to a charge‐selective interface) has been well studied for single‐phase mixed conductors (e.g., liquid electrolyte), but multiphase CP has been rarely addressed in literature. In our recent publication, we proposed that CP above certain threshold currents can flip the phase distribution in multiphase ion‐intercalation nanofilms sandwiched by ion‐blocking electrodes. This phenomenon is known as multiphase polarization (MP). It is then proposed that MP can further lead to nonvolatile interfacial resistive switching (RS) for asymmetric electrodes with ion‐modulated electron transfer, which theory can reproduce the experimental results of LTO memristors. In this study, a comprehensive 2D phase‐field model is derived for coupled ion‐electron transport in ion‐intercalation materials, with surface effects including electron transfer kinetics, non‐neutral wetting, energy relaxation, and surface charge. Then, the model is used to study MP. Time evolution of phase boundaries is presented, and analyze the switching time, current, energy, and cyclic voltammetry, for various boundary conditions. It is found that the switching performance can be improved significantly by manipulating surface conditions and mean concentration. Finally, the prospects of MP‐based memories and possible extensions of the current model is discussed.

Research on BIM collaborative design for the outdoor integrated pipeline of a rail transit depot

The outdoor integrated pipelines of rail transit depots have many specialties, many interfaces, and complex cross-relationships, which are the key and difficult points of depot design. The traditional outdoor integrated pipeline design method has the disadvantages of a large amount of data calculation, error-prone, and low drawing efficiency. At present, the use of BIM technology for auxiliary design also has difficulties, such as slow modeling speed, inconvenient collaborative design, and low efficiency of 3D conversion of 2D drawings. Based on Revit software, this paper focuses on the specific implementation scheme of BIM collaborative design of outdoor integrated pipelines in depots to solve the appealing problem. Overcame a number of key technologies independently developed, such as depot family library construction, Dynamo visual programming track rapid modeling, and GLS rapid drawing software. Realization of outdoor Comprehensive pipeline rapid modeling, collision optimization, and 2D rapid plotting. And it has been applied in an overhaul and heavy repair depot in the southwest, which has greatly improved the design efficiency and quality of outdoor integrated pipelines. The research result can provide a theoretical reference for the BIM collaborative design of the outdoor integrated pipeline of the depot.

The fluid flow modeling procedure including a critically stressed fracture analysis of coalbed methane reservoir: a case study of Upper Silesian Coal Basin, Poland

The geomechanical modeling turned out to be an essential component of the hydrocarbon exploration assisting reduction of risk of drilling issues and optimization of hydraulic fracturing treatment. This study provides a workflow of critically stressed fracture (CSF) analysis dedicated for coal layers. The main focus of the paper is applying the 1D mechanical models and following modelling of hydraulic fracturing treatment to describe the fracture behavior under the impact of the stresses at the wellbore scale. Another objective of the presented study is demonstration of benefits of 1D and 3D CSF analysis to understand fracture contribution to gained volume of hydrocarbon after fracturing of coal seam. Interpretation of fracture orientation and their behavior is vital to effective development of coal bed methane (CBM) resources as the CSF can be responsible for considerable part of CBM production. Natural fractures and faults contribute to fluid flow through rock. It is often noted that natural fractures may not be critically stressed at ambient stress state. However, during stimulation, the optimally oriented natural fracture sets have the inclination to become critically stressed. Hence, understanding of the recent stress state and fracture orientations is significant for well planning and fracturing design. The outcome of this study are comprehensive 1D mechanical Earth models (MEMs) for analyzed wells and explanation of behavior of identified CSF under variable stress state as well as understanding of the connectivity of natural fractures within zone subjected to fracturing treatment.

Score Function for the Optimization of the Performance of Forward Fill/Flush Differential Flow Modulation for Comprehensive Two-Dimensional Gas Chromatography.

Modulation is the key element of the comprehensive 2D gas chromatography separation. Forward fill/flush flow modulation is cost effective, robust and suitable for analysis of a wide range of samples. Even though this modulation system is well known, studies regarding its optimization are sparse. In this work, based on hundreds of experiments involving multiple column sets and modulation conditions, an approach was proposed that permits to facilitate the choice of the forward fill/flush flow modulation parameters. A score function was developed that allows to predict the forward fill/flush flow modulation process efficiency as judged by the modulated peak shape. The score function was based on the physical rules for optimized and quantitative forward fill/flush flow modulation proposed in our previous work, which state that the sum of the fill and flush modulation distances should be close to the modulation channel length and that the ratio of the flush and fill distances should be sufficiently high for efficient channel flushing. The score function was embedded in a freely available tool in the form of a forward fill/flush flow modulation calculator, which allows the user either to quickly check the relevancy of the modulation operating conditions or to obtain a suggestion for optimal modulation parameters.

Comprehensive 2D Chromatography

Comprehensive 2D Chromatography

Validation of the liquid chromatography-comprehensive multidimensional gas chromatography-time-of-flight mass spectrometer/flame ionization detector platform for mineral oil analysis exploiting interlaboratory comparison data

Mineral oils, classified into two main fractions, namely saturated (MOSH) and aromatic hydrocarbons (MOAH), originate from petroleum. Their determination in food is challenging due to the difficulty of isolating them from the matrix and the presence of natural interferences, leading to low reproducibility of the results among different laboratories. Therefore, standardized procedures are highly required to minimize the uncertainty caused by various sources (e.g., integration, interference removal, etc.). However, at present, a few sample preparation procedures have been standardized, while the analytical determination is mainly performed using the hyphenated liquid-gas chromatographic technique coupled with a flame ionization detector (LC-GC-FID). However, LC-GC-FID is still not enough for confirmatory purposes, for which the use of comprehensive 2D GC (GC × GC) has been suggested. Recently, the use of a fully integrated platform for routine and confirmatory purposes has been proposed by Bauwens and co-workers (2022), namely LC-GC × GC-time-of-flight mass spectrometer (ToFMS)/FID.

Curcumin-Loaded PnBA-b-POEGA Nanoformulations: A Study of Drug-Polymer Interactions and Release Behavior.

The current study focuses on the development of innovative and highly-stable curcumin (CUR)-based therapeutics by encapsulating CUR in biocompatible poly(n-butyl acrylate)-block-poly(oligo(ethylene glycol) methyl ether acrylate) (PnBA-b-POEGA) micelles. State-of-the-art methods were used to investigate the encapsulation of CUR in PnBA-b-POEGA micelles and the potential of ultrasound to enhance the release of encapsulated CUR. Dynamic light scattering (DLS), attenuated total reflection Fourier transform infrared (ATR-FTIR), and ultraviolet-visible (UV-Vis) spectroscopies confirmed the successful encapsulation of CUR within the hydrophobic domains of the copolymers, resulting in the formation of distinct and robust drug/polymer nanostructures. The exceptional stability of the CUR-loaded PnBA-b-POEGA nanocarriers over a period of 210 days was also demonstrated by proton nuclear magnetic resonance (1H-NMR) spectroscopy studies. A comprehensive 2D NMR characterization of the CUR-loaded nanocarriers authenticated the presence of CUR within the micelles, and unveiled the intricate nature of the drug-polymer intermolecular interactions. The UV-Vis results also indicated high encapsulation efficiency values for the CUR-loaded nanocarriers and revealed a significant influence of ultrasound on the release profile of CUR. The present research provides new understanding of the encapsulation and release mechanisms of CUR within biocompatible diblock copolymers and has significant implications for the advancement of safe and effective CUR-based therapeutics.

Combined experimental and theoretical studies of bis-chalcone: Estimation of non-covalent interactions

A new bischalcone BCH (2E,2′E)-1,1′-(((1,4-phenylenebis(methylene))bis(oxy))bis(2,1-phenylene))bis(3-(4-(benzyloxy)phenyl)prop‑2-en-1-one) has been synthesized and characterized by spectroscopic and single crystal X-ray diffraction techniques. The C–H···O and C–H···π intermolecular non-covalent interactions play crucial contribution in the formation of supramolecular architecture. A comprehensive Hirshfeld surface analysis and 2D fingerprint plots reveal the presence of intermolecular non-covalent interactions and percentage contributions of individual atoms. Hirshfeld energy framework calculations demonstrate dominance of dispersion energy. DFT calculations have been carried out energetic evaluation of non-covalent interactions. The charge distribution is rationalized by MEP surfaces. NCI Plot and QTAIM analysis have been computed to quantification of non-covalent interactions in the stabilization of the molecular crystal packing.

Stictamycin, an Aromatic Polyketide Antibiotic Isolated from a New Zealand Lichen-Sourced Streptomyces Species.

Here we describe the isolation and characterization of stictamycin, a new aromatic polyketide with activity against Staphylococcus aureus. Stictamycin was identified following metabolic profiling and bioactivity guided fractionation of organic extracts from Streptomyces sp. 438-3, an isolate from the New Zealand lichen Sticta felix. Comprehensive 1D and 2D NMR analyses were performed to determine the planar structure of stictamycin and relative configurations of stereo centers, with subsequent comparison of experimental and theoretical ECD spectra allowing elucidation of the absolute configuration. Whole-genome sequencing and biosynthetic gene cluster (BGC) analysis revealed that the Streptomyces sp. 438-3 strain contains an atypical type II polyketide (T2PKS) BGC capable of assembling polycyclic-aromatic ring skeletons. Cloning and knockout studies of this T2PKS BGC were used to confirm that it is responsible for the biosynthesis of stictamycin and elucidate a plausible biosynthetic scheme.

A comprehensive pyrolysis model for lignocellulosic biomass particles with a special emphasis on the anisotropic characteristics

The porous and fibrous structural tissue of lignocellulosic biomass serves as a transport channel for water and nutrients along the growth direction, indicating a highly anisotropic nature of biomass. The anisotropies of the thermal and structural properties of biomass have substantial influences on particle-scale reactions, transport processes, and morphological evolution during thermal conversions. An in-depth investigation of the anisotropic characteristics of these physicochemical phenomena in pyrolysis benefits in the understanding of biomass gasification and combustion processes. In this study, a comprehensive 2D axisymmetric mathematical model is developed to quantitatively analyze the pyrolysis behaviors of a cylindrical wood particle with or without anisotropy. Correlative unsteady energy and mass conservation equations are combined with a multistep kinetic model of biomass devolatilization. To improve the numerical descriptions of volatiles flowing in a porous biomass matrix, the constitutive equations of the Brinkman equation and dusty gas model are adopted. Moreover, a binary differential equation is used to calculate the simultaneous changes in the pore structure and shrinkage of the wood particles. When considering anisotropy, validations of the model against literature data demonstrate that it can reliably predict the intraparticle temperature profiles, weight loss, and particle shrinking degree of lignocellulosic biomass. Using this model, the coupling effects of multi-physical fields and reactions inside pyrolyzing wood particles are explored. It is revealed that the anisotropic characteristics of biomass influence not only the orientations of intraparticle heat and mass transport processes but also their mechanisms, resulting in varying degrees of secondary reactions and particle shrinkage.

Three new pentacyclic triterpenes isolated from Strychnos henningsii Gilg. and their cytotoxic evaluation

Three new pentacyclic triterpenes, henninglupal (3), 19-ethylene henningsyl (4), and 19-ethylene henningsal (6), along with the previously reported crystal heninngsal (2) and alpha-amyrin acetate (5) were isolated from a methanolic extract of the bark of Strychnos henningsii Gilg. The new pentacyclic triterpenes were elucidated through comprehensive spectroscopic analysis, including 1D, 2D NMR, and High-resolution LCMS. The in vitro MTT cytotoxicity of compound 2 – 6 was evaluated on Caco-2 cell lines, where all the isolated compounds exhibited low cytotoxic effects up to concentrations of 125 µM.

Skullcapflavone II, a novel NQO1 inhibitor, alleviates aristolochic acid I-induced liver and kidney injury in mice.

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (KD = 4.198 μmol/L) and inhibitory activity (IC50 = 2.87 μmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect.

Friedolanostanes from Garcinia benthamii Pierre: in silico Investigation of Anti-inflammatory Activity Targeting the NF-κB p50 Subunit

An investigation of the chemical constituents present in the dichloromethane (DCM) extracts of rind, fruit, roots and leaves of Garcinia benthamii Pierre has led to an isolation of a new triterpene (24E)-23-acetoxy-3α- hydroxylanosta-9(11),16,24-trien-26-oic acid (1), squalene and triacylglycerols from the roots; methyl (24E)- 3α,9α,23-trihydroxy-17,14-friedolanosta-14,24-dien-26-oate (2), caryophyllene, squalene, a mixture of compound 1, (22Z,24E)-9α-hydroxy-3-oxo-17,14-friedolanosta-14,22,24-trien-26-oic acid (3) and another new triterpene (24E)-9α-hydroxy-3-oxo-17,14-friedolanosta-14,24-dien-26-oic acid (4) derived from pericarp; a combination of compound 3 and the new isolated triterpene methyl (24E)-9α,23-dihydroxy-3-oxo-17,14- friedolanosta-14,24-dien-26-oate (5), triacylglycerols, friedelin, squalene and a mixture of β-sitosterol and stigmasterol accrued from the outer covering of the stalk; compound 2, caryophyllene, α-carotene and chlorophyll a originating from the leaves; compound 2 and a blend of β-sitosterol and stigmasterol from the blooms; δ-tocotrienol, squalene and triacylglycerols from the mesocarp; and triacylglycerols and a composite of stigmasterol and β-sitosterol recovered from the seeds of G. benthamii. The molecular orientation of compound 1 was characterized by comprehensive 1D and 2D NMR examinations while compounds 2-5 were elucidated by 1D NMR spectroscopy since a new triterpene 4 was observed to have a small difference with compound 3 in C-22 and compound 5 was observed to have a difference with the C-3 signal of compound 2. To further examine the possible bioactivities of the friedolanostanes especially the new molecules, the anti-inflammatory potential of these compounds was predicted through docking analysis in Autodock Vina. Four of the identified friedolanostanes (2-5) were found to have higher binding affinities to NF-κB p50 homodimer than the control dexamethasone. Considering all the probable interactions of 9 amino acid residues, (Arg 57, Tyr 60, Glu 63, Lys 244, Pro 246, Lys 275, Arg 308, Gln 309 and Phe 310) perceivable binding mechanisms were observed to actively interact with the compounds either by conventional hydrogen bonding or by van der Waals forces. Further confirmation from the molecular dynamics study revealed that the stability of the protein-ligand complexes with compounds 2-5 had no significant conformational changes in the structure of the p50 homodimer. Hence, this study provided a chemical profile of the DCM extract obtained from the plant and propose a potential anti-inflammatory activity of the friedolanostanes through in silico investigation. Friedolanostanes (2-5)with promising anti-inflammatory activity may be synthesized and subjected to in vitro and in vivo investigation to establish the anti-inflammatory properties.

Headspace solid-phase microextraction comprehensive 2D gas chromatography-time of flight mass spectrometry (HS-SPME-GC × GC-TOFMS) for origin traceability of the genus Hymenaea resinites.

Differentiating the chemical compositions of resinite (amber, copal, and resin) is very crucial for determining the botanical origin and chemical compositions of the fossilised amber and copal. This differentiation also assists in understanding the ecological functions of resinite. Headspace solid-phase microextraction-comprehensive two-dimensional (2D) gas chromatography-time-of-flight mass-spectroscopy (HS-SPME-GC × GC-TOFMS) was firstly proposed and utilised in this research to investigate the chemical components (volatile and semi-volatile compositions) and structures of Dominican amber, Mexican amber, and Colombian copal for origin traceability, which were all produced by trees belonging to the genus Hymenaea. Principal component analysis (PCA) was used to analyse the relative abundances of each compound. Several informative variables were selected, such as caryophyllene oxide, which was only found in Dominican amber, and copaene, which was only found in Colombian copal. 1H-Indene, 2,3-dihydro-1,1,5,6-tetramethyl- and 1,1,4,5,6-pentamethyl-2,3-dihydro-1H-indene were abundantly present in Mexican amber, which were the critical fingerprints for the origin traceability of amber and copal produced by trees from the genus Hymenaea of various geological places. Meanwhile, some characteristic compounds were closely related to the invasion of fungi and insects; their links with ancient fungi and insect categories were also decoded in this study and these special compounds could be used to further study the plant-insect interactions.

Discovery of New Triterpenoids Extracted from Camellia oleifera Seed Cake and the Molecular Mechanism Underlying Their Antitumor Activity.

Theasaponin derivatives, which are reported to exert antitumor activity, have been widely reported to exist in edible plants, including in the seed cake of Camellia oleifera (C.), which is extensively grown in south of China. The purpose of this study was to isolate new theasaponin derivatives from C. seed cake and explore their potential antitumor activity and their underlying molecular mechanism. In the present study, we first isolated and identified four theasaponin derivatives (compounds 1, 2, 3, and 4) from the total aglycone extract of the seed cake of Camellia oleifera by utilizing a combination of pre-acid-hydrolysis treatment and activity-guided isolation. Among them, compound 1 (C1) and compound 4 (C4) are newly discovered theasaponins that have not been reported before. The structures of these two new compounds were characterized based on comprehensive 1D and 2D NMR spectroscopy and high-resolution mass spectrometry, as well as data reported in the literature. Secondly, the cytotoxicity and antitumor property of the above four purified compounds were evaluated in selected typical tumor cell lines, Huh-7, HepG2, Hela, A549, and SGC7901, and the results showed that the ED50 value of C4 ranges from 1.5 to 11.3 µM, which is comparable to that of cisplatinum (CDDP) in these five cell lines, indicating that C4 has the most powerful antitumor activity among them. Finally, a preliminary mechanistic investigation was performed to uncover the molecular mechanism underlying the antitumor property of C4, and the results suggested that C4 may trigger apoptosis through the Bcl-2/Caspase-3 and JAK2/STAT3 pathways, and stimulate cell proliferation via the NF-κB/iNOS/COX-2 pathway. Moreover, it was surprising to find that C4 can inhibit the Nrf2/HO-1 pathway, which indicates that C4 has the potency to overcome the resistance to cancer drugs. Therefore, C1 and C4 are two newly identified theasaponin derivatives with antitumor activity from the seed cake of Camellia oleifera, and C4 is a promising antitumor candidate not only for its powerful antitumor activity, but also for its ability to function as an Nrf2 inhibitor to enhance the anticancer drug sensitivity.

Chemical investigation of Buddleja officinalis leaves and localization of defensive triterpenoids to its glandular trichomes

Buddleja officinalis is a traditional Chinese medicinal plant covered with glandular and non-glandular trichomes on leaves. Phytochemical investigation of its leaves led to the identification of one undescribed tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic acid (1) and one first identified natural product tetranorcycloartane 3-oxo-25,26,27,29-tetranorcycloartan-24-oic methyl ester (2), along with an undescribed megastigmane glucoside (3) and 14 known constituents (4–17). Structures of undescribed chemicals were elucidated by comprehensive 1D and 2D NMR, MS and CD analysis. Further chemical investigation resulted in six triterpenoids (4–9) being localized to the trichomes of B. officinalis. The major trichome components cycloeucalenone (4) and 24-oxo-29-norcycloartan-3-one (5) showed potent antifeedant activity against a generalist insect cotton bollworm (Helicoverpa armigera), but no obvious activity against the specialist herbivore Hyphasis inconstans. Compounds 4 and 7 also displayed inhibitory effects on seed germination of Arabidopsis thaliana. In addition, 1 and 4 exhibited moderate antibacterial activity toward three gram-positive bacteria.

Bioactive Alkaloids from the Marine-Derived Fungus Metarhizium sp. P2100.

The Metarhizium fungal species are considered the prolific producers of bioactive secondary metabolites with a variety of chemical structures. In this study, the biosynthetic potential of marine-derived fungus Metarhizium sp. P2100 to produce bioactive alkaloids was explored by using the one strain many compounds (OSMAC) strategy. From the rice solid medium (mixed with glucose peptone and yeast broth (GPY)), wheat solid medium (mixed with Czapek) and GPY liquid medium, one rare N-butenone spiroquinazoline alkaloid, N-butenonelapatin A (1), together with nine known compounds (2-10), were isolated and identified. Their structures were elucidated by analysis of the comprehensive spectroscopic data, including 1D and 2D NMR and HRESIMS, and the absolute configuration of 1 was determined by a single-crystal X-ray crystallographic experiment. N-butenonelapatin A (1) represents the first example of N-butenone spiroquinazoline with a rare α, β-unsaturated ketone side chain in the family of spiroquinazoline alkaloids. Compound 4 displayed antibacterial activity against Vibrio vulnificus MCCC E1758 with a minimum inhibitory concentration (MIC) value of 6.25 µg/mL. Compound 7 exhibited antibacterial activities against three aquatic pathogenic bacteria, including V. vulnificus MCCC E1758, V. rotiferianus MCCC E385 and V. campbellii MCCC E333 with the MIC values of 12.5, 12.5 and 6.25 μg/mL, respectively. Compounds 3 and 6 demonstrated anti-inflammatory activity against NO production induced by lipopolysaccharide (LPS) with the IC50 values of 37.08 and 37.48 μM, respectively. In addition, compound 1 showed weak inhibitory activity against the proliferation of tumor cell lines A-375 and HCT 116. These findings further demonstrated that fungi of the Metarhizium species harbor great potentials in the synthesis of a variety of bioactive alkaloids.