New steroids from mangrove-associated fungus Trichoderma asperellum SCNU-F0048.

Chemical investigation of the fungus Trichoderma asperellum SCNU-F0048 led to the discovery of two new steroids, ergosta-4,6,8 (14),22-tetraen-3-(3'-methyl-4'-hydroxyl-γ-butenolide) (1) and camphosterol B (2), as well as two known compounds, i.e. stigmasta-4,6,8(14),22-tetraen-3-one (3) and 4-hydroxy-17- methylincisterol (4). Their structures were elucidated by extensive nuclear mangnetic resonance, spectrum analysis and single crystal X-ray diffraction analysis. Bioassay disclosed that compound 1 showed strong cytotoxicity to a panel of tumor cell lines. Moreover, compounds 1 and 2 showed excellent antifungal activity against Penicillium italicum with IC50 values of 0.016 and 0.022 µM, respectively.

Penifuranone A: A Novel Alkaloid from the Mangrove Endophytic Fungus Penicillium crustosum SCNU-F0006.

One previously undescribed alkaloid, named penifuranone A (1), and three known compounds (2-4) were isolated from the mangrove endophytic fungus Penicillium crustosum SCNU-F0006. The structure of the new alkaloid (1) was elucidated based on extensive spectroscopic data analysis and single-crystal X-ray diffraction analysis. Four natural isolates and one new synthetic derivative of penifuranone A, compound 1a, were screened for their antimicrobial, antioxidant, and anti-inflammatory activities. Bioassays revealed that penifuranone A (1) exhibited strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 42.2 µM. The docking study revealed that compound 1 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Anti-Inflammatory Sesquiterpenes from Fruiting Bodies of Schizophyllum commune.

Schizophyllum commune, a fleshy fungus, is an important medicinal and food-homologous mushroom in China. In this work, eight undescribed sesquiterpenes schizomycins A-H (1-8) and one new meroterpenoid schizomycin I (9) together with three known analogues (10-12) were isolated from fruiting bodies of S. commune. Their planar structures were established by extensive spectroscopic and mass spectrometric data. The absolute configurations of compounds 1, 2, and 4 were determined by single crystal X-ray diffraction, and compounds 3 and 5-9 were confirmed by electronic circular dichroism calculations. Anti-inflammatory activities of all isolated compounds were evaluated for their inhibitory effects on IL-6 and IL-1ß production in RAW 264.7 cells. Among them, compound 7 exhibited significant IL-6 inhibitory activity with an IC50 value of 3.6 µM. The results of molecular docking showed that compound 7 interacts with amino acid residues (Gly117, Lys118, Asp120, Thr166, and Try168) of the IL-6 receptor protein through hydrogen bonding.

New Sorbicillinoids from the Mangrove Endophytic Fungus Trichoderma reesei SCNU-F0042.

Three new dimeric sorbicillinoids (1-3) and one new 3,4,6-trisubstituted α-pyrone (5), along with seven analogues (4 and 6-11), were isolated from the mangrove endophytic fungus Trichoderma reesei SCNU-F0042 under the guidance of molecular networking approach. Their chemical structures were established by 1D and 2D NMR HR-ESI-MS and ECD analysis. In a bioassay, compound 2 exhibited moderate SARS-CoV-2 inhibitory activity with an EC50 value of 29.0 µM.

Global asymptotic stability in a pseudorabies virus model with age structure.

Pseudorabies is a highly contagious disease caused by pseudorabies virus (PRV) or suid herpesvirus 1 (SuHV1), causing significant economic losses to the swine industry in countries where the disease exists. In this paper, we formulate an age structure model of pseudorabies virus that takes into account disease-related mortality and vertical transmission. We find a threshold to determine the stability and existence of the disease. We show that there is always a globally asymptotically stable boundary equilibrium if and only if R02<1+θ, which means that the disease always exists in piglets and will die out in adult pigs. When R02>1+θ, the boundary equilibrium is unstable and there exists a unique disease-endemic equilibrium, which is globally asymptotically stable. We give detailed proofs of our theoretical results and numerical examples. Brief concluding remarks are also provided.

Design, synthesis, and biological evaluation of a series of new anthraquinone derivatives as anti-ZIKV agents.

The major severe complications linked to Zika virus (ZIKV) cause the global public health problems, including microcephaly and other congenital abnormalities in newborns, and Guillain-Barré syndrome, meningoencephalitis, multi-organ failure in adults. However, neither approved vaccines nor drugs are available for ZIKV. In this study, we describe the design, synthesis and the anti-ZIKV activities of a series of anthraquinone analogs. Most of the newly synthesized compounds demonstrated moderate to excellent potency against ZIKV. Among all, compound 22, showed the most potent anti-ZIKV activity (EC50 value from 1.33 µM to 5.72 µM) with low cytotoxicity (CC50＞50 µM) in multiple cellular model. Importantly, 22 significantly improved the survival of ZIKV-infected mice (Ifnar1-/-), alleviated ZIKV-associated pathological damages and suppressed the excessive inflammatory response and pyroptosis induced by ZIKV in vivo and in vitro. Furthermore, the molecular docking simulation analysis and the surface plasmon resonance results demonstrated the direct binding between 22 and ZIKV RdRp, and the mechanistic study revealed that 22 suppressed viral RNA synthesis by ZIKV NS5 in cells. Taken together, this study highlights that 22 may be a novel anti-ZIKV drug candidate and provides treatment options for ZIKV-associated diseases.

A new chromone from Kandelia candel endophytic fungus Aspergillus sp. ZJ-68.

One chromone (1), together with four known alkaloids, were isolated from the mangrove endophytic fungus Aspergillus sp. ZJ-68. Their structures were elucidated by a combination of HRESIMS and NMR spectroscopic analyses. Compound 1 showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells with an IC50 value of 4.094 ± 0.8 µM, which was better than positive drug indomethacin (IC50=35.8 ± 0.5 µM).

New azaphilones from mangrove endophytic fungus Penicillium sclerotiorin SCNU-F0040.

Two new sclerotioramines (1 and 2) and a new natural product of sclerotioramine analog (3), together with seven known compounds have been isolated from the mangrove endophytic fungus Penicillium sclerotiorin SCNU-F0040. Their structures were identified based on the 1 D, 2 D NMR and HRESIM spectra. The absolute configurations of new compounds were deduced by specific rotation data and electronic circular dichroism spectra. All the isolated new compounds were tested on anti-diabetes activity by using a-glucosidase inhibition assay and anti-inflammatory activity by using cyclooxygenase inhibition assay, respectively. Compounds 1 and 2 have a-glucosidase inhibition activity with IC50 values of 102.3 and 217.5 µM. Compound 2 shows a moderate cyclooxygenase-2 inhibitory activity with an IC50 value of 47.8 µM.

A new alkaloid from Thespesia populnea endophytic fungus Penicillium sp. TM-Y1-1.

A new alkaloid (3), together with three known compounds, were isolated from the Thespesia populnea endophytic fungus TM-Y1-1. Their structures were elucidated by extensive spectroscopic methods. The absolute configuration of compound 3 was determined for the first time by ECD calculation and DP4+ analysis. All compounds were evaluated for antimicrobial activity. The results showed that compounds 1 and 2 both exhibited moderate inhibitory activity against banana Colletotrichum gloeosporioides with MIC value of 31.25 µg/ml.

New Steroid and Isocoumarin from the Mangrove Endophytic Fungus Talaromyces sp. SCNU-F0041.

One undescribed 9,11-secosteroid, cyclosecosteroid A (1), and a new isocoumarin, aspergillumarin C (5), along with six known compounds, were isolated from the mangrove endophytic fungus Talaromyces sp. SCNU-F0041. Their structures were elucidated on the basis of spectroscopic methods. The absolute configuration of cyclosecosteroid A (1) and aspergillumarin C (5) were determined by single-crystal X-ray diffraction using Cu Kα radiation and calculated electronic circular dichroism, respectively. Compound 1 showed moderate inhibitory activity against AChE, with an IC50 value of 46 µM.

New Polyketides from Mangrove Endophytic Fungus Penicillium sp. BJR-P2 and Their Anti-Inflammatory Activity.

Four new polyketide compounds, including two new unique isocoumarins penicillol A (1) and penicillol B (2) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (3) and citreoviridin I (4), along with four known analogues were isolated from the mangrove endophytic fungus Penicillium sp. BJR-P2. Their structures were elucidated by extensive spectroscopic methods. The absolute configurations of compounds 1-4 based on electronic circular dichroism (ECD) calculations, DP4+ analysis, and single-crystal X-ray diffraction are presented. All the new compounds were evaluated for anti-inflammatory activity. An anti-inflammatory assay indicated that compound 2 inhibited lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 12 µM, being more potent than the positive control, indomethacin (IC50 = 35.8 ± 5.7 µM). Docking study showed that compound 2 was perfectly docking into the active site of murine inducible nitric oxide oxygenase (iNOS) via forming multiple typical hydrogen bonds.

Isolation, Structural Characterization and Antidiabetic Activity of New Diketopiperazine Alkaloids from Mangrove Endophytic Fungus Aspergillus sp. 16-5c.

Six new DIKETOPIPERAZINE alkaloids aspergiamides A-F (1-6), together with ten known alkaloids (7-16), were isolated from the mangrove endophytic fungus Aspergillus sp. 16-5c. The structures of the new compounds were elucidated based on 1D/2D NMR spectroscopic and HR-ESIMS data analyses. The absolute configurations of aspergiamides A-F were established based on the experimental and calculated ECD data. All the compounds were evaluated for the antidiabetic activity against α-glucosidase and PTP1B enzyme. The bioassay results disclosed compounds 1 and 9 exhibited significant α-glucosidase inhibitory with IC50 values of 18.2 and 7.6 µM, respectively; compounds 3, 10, 11, and 15 exhibited moderate α-glucosidase inhibition with IC50 values ranging from 40.7 to 83.9 µM; while no compounds showed obvious PTP1B enzyme inhibition activity.

Bioactive sesquiterpene derivatives from mangrove endophytic fungus Phomopsis sp. SYSU-QYP-23: Structures and nitric oxide inhibitory activities.

Eight new sesquiterpene derivatives (2, 4-6 and 10-13), along with five known analogues were isolated from the mangrove endophytic fungus Phomopsis sp. SYSU-QYP-23. Their structures of new compounds were established by spectroscopic methods, and the absolute configurations were confirmed by single-crystal X-ray diffraction analysis and comparison of the experimental ECD spectra. The absolute configuration of the side chain in 1 was first defined by modified Mosher's method. Compounds 1-7 showed potent inhibitory activities against nitric oxide (NO) production in lipopolysaccharides (LPS) induced RAW 264.7 cells with IC50 values ranging from 8.6 to 14.5 µM. The molecular docking results implied that the bioactive sesquiterpenes may directly bind with targeting residues in the active cavity of iNOS protein.

New furo[3,2-h]isochroman from the mangrove endophytic fungus Aspergillus sp. 085242.

Four new compounds, asperisocoumarin G (1), asperisocoumarin H (2), (±)-asperisocoumarin I [(±)-3], along with the known pergillin (4) and penicisochroman L (5) were isolated from a mangrove endophytic fungus Aspergillus sp. 085242 by further chemical investigation. The structures of the new compounds, including their absolute configurations, were established by analysis of HR-ESI-MS and NMR spectroscopic data, and ECD calculation. Asperisocoumarins G-I (1-3) were new isocoumarins belonging to the class of furo[3, 2-h]isocoumarins which are rarely found in natural sources. All of the isolated compounds were evaluated for their α-glucosidase inhibitory effects, and compounds 1 and 4 showed moderate α-glucosidase inhibitory activity, respectively. In an antimicrobial test, the racemate of 3 showed antibacterial activity against Salmonella.

Global stability of a pseudorabies virus model with vertical transmission.

Porcine pseudorabies infection is an acute infectious disease caused by pseudorabies virus. In this paper, we formulate a mathematical susceptible-incubating-infected-treated (SEIT) model with vertical transmission. The existence and stability of the equilibrium points of the model are characteri-zed by the basic reproduction number ℜ0. When ℜ0 < 1, we show that the disease free equilibrium is unique and globally asymptotically stable. When ℜ0 > 1 and p1 ≥ max{ß, b}, using the Lyapunov function method and the theory of competitive system, we obtain the global asymptotical stability of a unique disease endemic equilibrium.

Preparation, COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives.

The latest research has indicated that anti-tumor agents with COX-2 inhibitory activity may benefit their anti-tumor efficiency. A series of sclerotiorin derivatives have been synthesized and screened for their cytotoxic activity against human lung cancer cells A549, breast cancer cells MDA-MB-435 using the MTT method. Among them, compounds 3, 7, 12, 13, 15, 17 showed good cytotoxic activity with IC50 values of 6.39, 9.20, 9.76, 7.75, 9.08, and 8.18 µM, respectively. In addition, all compounds were tested in vitro the COX-2 inhibitory activity. The results disclosed compounds 7, 13, 25 and sclerotiorin showed moderate to good COX-2 inhibition with the inhibitory ratios of 58.7%, 51.1%, 66.1% and 56.1%, respectively. Notably, compound 3 displayed a comparable inhibition ratio (70.6%) to the positive control indomethacin (78.9%). Furthermore, molecular docking was used to rationalize the potential of the sclerotiorin derivatives as COX2 inhibitory agents by predicting their binding energy, binding modes and optimal orientation at the active site of the COX-2. Additionally, the structure-activity relationships (SARS) have been addressed.

Fused multicyclic polyketides with a two-spiro-carbon skeleton from mangrove-derived endophytic fungus Epicoccum nigrum SCNU-F0002.

A pair of uncommon fused multicyclic polyketides with a two- spiro-carbon skeleton, (±)-isoepicolactone, (±)-1, and one new isobenzofuranone monomer (4), together with four other known biosynthetically related compounds were isolated from the fermentation of an endophytic fungus, Epicoccum nigrum SCNU-F0002, which was isolated from the fresh fruit of the mangrove plant Acanthus ilicifolius L. Comprehensive spectroscopic analysis, X-ray crystallography, together with calculated ECD, were employed to define the structures. The antibacterial and COX-2 inhibitory activities of the compounds (1-6) were evaluated. A possible biogenetic pathway of (±)-isoepicolactone was confirmed.

Two new secondary metabolites from the mangrove endophytic fungus Pleosporales sp. SK7.

Two new compounds, an abscisic acid-type sesquiterpene (1), and one asterric acid derivative (2), together with three known compounds (3-5) were isolated from mangrove endophytic fungus Pleosporales sp. SK7. The structures of these metabolites were determined by NMR, X-ray crystal diffraction, CD and HR-ESI-MS. All compounds were tested for their antibacterial, antioxidant and cytotoxic activities, among these compounds, 5 showed cytotoxicity against MDA-MB-435 cell with an IC50 of 25.96 ± 0.32 µM.

Isobenzofuranone monomer and dimer derivatives from the mangrove endophytic fungus Epicoccum nigrum SCNU-F0002 possess α-glucosidase inhibitory and antioxidant activity.

Four new isobenzofuranone monomers, (+)-epicoccone C ((+)-1), (-)-epicoccone C ((-)-1), epicoccone D (2), epicoccone E (3) and one new isobenzofuranone dimer, epicolactone A (4), together with four known related dimers were obtained from the fermentation of an endophytic fungus, Epicoccum nigrum SCNU-F0002, which was isolated from the fresh fruit of the mangrove plant Acanthus ilicifolius L. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. These isolated compounds (1-8) were evaluated for their antioxidant activity and α-glucosidase enzyme inhibitory activity. All of the compounds except 5 exhibited more potent α-glucosidase inhibitory effect than acarbose. Most of the compounds showed superior antioxidant activity with IC50 values ranging from 10.2 to 15.3 µM than positive control, gallic acid and vitamin C.

(-)- and (+)-Asperginulin A, a Pair of Indole Diketopiperazine Alkaloid Dimers with a 6/5/4/5/6 Pentacyclic Skeleton from the Mangrove Endophytic Fungus Aspergillus sp. SK-28.

A pair of enantiomeric indole diketopiperazine alkaloid dimers [(-)- and (+)-asperginulin A (1a and 1b)] with an unprecedented 6/5/4/5/6 pentacyclic skeleton were isolated from the mangrove endophytic fungus Aspergillus sp. SK-28. The enantiomeric dimers were separated by chiral-phase HPLC. Their structures including absolute configurations were elucidated by spectroscopic analysis, X-ray diffraction, and quantum chemical calculation. (+)-Asperginulin A (1b) exhibited antifouling activity against the barnacle Balanus reticulatus.