Three new aspochalasin derivatives from the marine-derived fungus Spicaria elegans

Three new aspochalsins（R-T）（1-3） were isolated from the marine-derived fungus Spicaria elegans.Their structures were elucidated on the basis of comprehensive spectral analysis including 1D and 2D NMR techniques,and HR-ESI-MS.

A new naphthoquinoneimine derivative from the marine algal-derived endophytic fungus Aspergillus niger EN-13

Cultivation of an endophytic fungus Aspergillus niger EN-13 that was isolated from the inner tissue of the marine brown alga Colpomenia sinuosa resulted in the characterization of a new naphthoquinoneimine derivative, namely, 5,7-dihydroxy-2-[1-（4- methoxy-6-oxo-6H-pyran-2-yl）-2-phenylethylamino]-[ 1,4]naphthoquinone. The structure of the new compound was established on the basis of various NMR spectroscopic analyses including 2D NMR techniques, El-MS, and HR-ESI-MS. This compound displayed moderate antifungal activity.

The Cytotoxic Constituents from Marine-derived Streptomyces 3320^(#)

The present work studies the chemical constituents from marine-derived streptomyces 3320^# and their antitumor activities. The n-BuOH extract of the ferment broth of 3320^# was chromatographed on silica gel, Sephadex LH-20, ODS columns and HPLC to separate the compounds with antitoumor activities. Their structures were identified using IR, UV, NMR, MS spectroscopic techniques and compared with published data. The antitumor activities of the isolates were assayed using SRB method and flow cytometry assay, accompanied with the morphological observation of the cells under light micro- scope against mammalian tsFT210 cells. Ten compounds, cyclo-（Ala-Leu） 1, cyclo-（Ala-Ile） 2, cyclo-（Ala-Val） 3, cyclo- （Phe-Pro） 4, cyclo-（Phe-Gly）5, cyclo-（Leu-Pro）6, 1-methyl-1, 2, 3, 4-tetrahydro-β-carboline-3-carboxylic acid 7, N-（4- hydroxyphenethyl） acetamide 8, 4-methyoxy-l-（2-hydroxy） ethylbenzene 9 and uridine 10, were isolated from the ferment broth of streptomyces 3320^# . Among them, compounds 6, 7, 8 and 10 showed potent cytotoxicity against the tsFT210 cell with the IC50 values of 3.6, 7.2, 5.2 and 1.6 mmol L-1, respectively. Compounds 8, 10 also exhibited apoptosis inducing activity under 2.0 mmol L-1. Compounds 6, 7, 8 and 10 are the principle bioactive constituents responsible for the antitumor activities of marine streptomyces 3320^#. Compound 7 was isolated from this species for the first time.

Construction of a Metagenomic DNA Library of Sponge Symbionts and Screening of Antibacterial Metabolites

To study the bioactive metabolites produced by sponge-derived uncultured symbionts, a metagenomic DNA library of the symbionts of sponge Gelliodes gracilis was constructed. The average size of DNA inserts in the library was 20 kb. This library was screened for antibiotic activity using paper disc assaying. Two clones displayed the antibacterial activity against Micrococcus tetragenus. The metabolites of these two clones were analyzed through HPLC. The result showed that their metabolites were quite different from those of the host E. coli DNA and the host containing vector pHZ132. This study may present a new approach to exploring bioactive metabolites of sponge symbionts.

The Synthesis of Glycoglycerolipids

A convenient synthetic route was developed for the synthesis of the novel glycolipids: 1, 2-di-O-acyl-3-O-(2-acylamide-2-deoxy-a-D-glucopyranosyl)-sn-glycerols. 10 new compounds of glycolipids with different acyl groups were obtained.

Growth inhibition to three red tide microalgae by extracts of Ulva pertusa

Growth inhibition effect of different concentration of distilled water extract and four polar organic solvent (methanol, acetone, ether and chloroform) extracts of Ulva pertusa on three typical red tide microalgae (Heterosigma akashiwo, Alexandrium tamarense and Prorocentrum micans) were inves- tigated. Liquid-liquid fractionation and HPLC analysis for methanol extract of U. pertusa were carried out. Growth of the three microalgae was significantly inhibited by the distilled water extract of U. pertusa at relatively higher concentration. However, the cells of the three microalgae did not die completely even at high concentration. Methanol extract of U. pertusa showed the highest growth inhibition on the three mi- croalgae, and all the cells of the three microalgae were killed at relatively high concentration. The other three organic solvent extracts of U. pertusa had no apparent effect on the three microalgae. The results of bioassays and HPLC analysis suggested that the inhibitory substances in U. pertusa to the microalgal growth had relatively high polarities. H. akashiwo was the most sensitive one while A. tamarense was the most tolerant one to the growth inhibitory substances.

Chemical Characteristics and Anticoagulant Activities of Two Sulfated Polysaccharides from Enteromorpha linza (Chlorophyta)

Two sulfated polysaccharides, designated MP and SP, were extracted from the marine green alga Enteromorpha linza using hot water and then purified using ion-exchange and size-exclusion chromatography. The anticoagulant activities of MP and SP were examined by determination of their activated partial thromboplastin time （APTT）, thrombin time （TT） and prothrombin time （PT） using human plasma. Results showed that MP and SP were composed of abundant rhamnose with small amounts of xylose and glucuronic acid, whereas SP also contained a small amount of galactose. Approximate molecular weights of MP and SP were 535 and 502 kDa, respectively. As compared with SP, MP had higher contents of sulfate ester （19.0%） and uronic acid （14.9%）. The MP mainly consisted of （1→4）-linked rhamnose residues with partially sulfated groups at the C-3 position, and small amounts of （1→3, 4）-linked rhamnose, （1→2,4）-linked rhamnose, （1→4）-linked glucuronic acid and （1→4）-linked xylose residues. The SP contained abundant （1→4）-linked rhamnose with minor amounts of （1→3）-linked rhanmose, （1→3, 4）-linked rhamnose, （1→2, 4）-linked rhanmose, （1→4）4inked glucuronic acid, （1→4）-linked xylose, and （1→3）-linked galactose residues. The sulfate groups were mainly located at C-3 of （1→4）-linked rhamnose residues. Both MP and SP, in particular the former, effectively prolonged APTT and TT. This work demonstrates that MP and SP have unique structural characteristics distinct from those of other sulfated polysaccharides from Enteromorpha. The MP is a potential source of anticoagulant, and the difference in anticoagulant activities of the two sulfated polysaccharides is directly linked to the discrepancy of their chemical features.

Why is the beautyberry so colourful? Evolution,biogeography,and diversification of fruit colours in Callicarpa(Lamiaceae)

Fruit colour is essential to seed dispersal,speciation,and biological diversity in global ecosystems.The relationship between fruit-colour variation and species diversification has long been of interest in evolutionary biology,but remains poorly understood at the genus level.Here,we used Callicarpa,a typical representative of pantropical angiosperm,to analyse whether fruit colours are correlated with biogeographic distribution,dispersal events,and diversification rate.We estimated a time-calibrated phylogeny for Callicarpa and reconstructed ancestral fruit colour.Utilizing phylogenetic methods,we estimated the major dispersal events across the phylogenetic tree and the most likely fruit colours related to each dispersal event,and tested whether the dispersal frequencies and distances of the four fruit colours between major biogeographical areas were equal.We then tested whether fruit colours are correlated with latitude,elevation,and diversification rate.Biogeographical reconstructions showed that Callicarpa originated in the East Asia and Southeast Asia during the Eocene(-35.53 Ma) and diverse species diverged mainly in the Miocene and lasted into the Pleistocene.Large-scale dispersal events were significantly associated with violet-fruited lineages.Furthermore,different fruit colours were markedly correlated with different latitudes and elevations(e.g.,violet fruits were correlated with higher latitudes and elevations;red fruits and black fruits with lower latitudes;white fruits with higher elevations).Notably,violet fruits were statistically associated with highest diversification rates,driving fruit colour variation among different regions globally.Our results contribute to further understanding why fruit colour is so variable at the genus level of angiosperms in different areas around the world.

One-pot Synthesis of Divalent and Trivalent Cluster Mannosides via Ugi Four-component Reaction

The Ugi four-component reaction (U-4CR) was utilized to prepare divalent and trivalent cluster mannosides. Thus, two target compounds 6 and 8 were obtained efficiently using carboxymethyl 2, 3, 4, 6-tetra-O-acetyl--D-mannopyranoside 4 as acid component, and 1, 6-hexanediamine or tris(2-aminoethyl)amine as the multivalent scaffolds.

Ab Initio Prediction of ^(29)Si-NMR Chemical Shifts

The ability of several ab initio models to predict experimental 29Si-NMR chemical shift is examined. The shielding values of trimethylsilyl chloride (A), t-butyldimethylsilyl chloride (B) and allyltrimethylsilane (C) are calculated by GIAO , CSGT and IGAIM methods, using HF/6-31G*, B3LYP/6-31G*, HF/6-311+G **, B3LYP/6-311+G ** and MPW1PW91/6-311+G ** models respectively. The 29Si chemical shifts calculated by GIAO method using HF/6-311+G ** model are highly in agreement with those obtained experimentally. All of the models above reproduce the trends of chemical shifts in all cases studied, suggesting that the models are of practical value.

Two new olean-type triterpene fatty esters from Scorzonera mongolica

Two new triterpene fatty esters, 3β-tetradecanoyl moradiol 1 and 3β-dodecanoyl moradiol 2, were isolated from Scorzonera mongolica. Their structures were elucidated as 3β-tetradecanoyloxy-28-hydroxylolean-18-ene and 3β-dodecanoyl-28-hydroxyl-olean-18-ene on the basis of IR, MS, 1D NMR and extensive 2D NMR spectroscopic analyses.

A New α-Cyclopiazonic Acid Alkaloid Identified from the Weizhou Island Coral-Derived Fungus Aspergillus flavus GXIMD 02503

A new oxygenated tricyclic cyclopiazonic acid(CPA)alkaloid,asperorydine Q(1),along with seven known compounds,namely,asperorydines O(2)and J(3),speradine H(4),cyclopiamides A(5)and H(6),saadamysin(7),and pyrazinemethanol(8),were isolated from the coral-associated Aspergillus flavus GXIMD 02503.The structures were elucidated by physicochemical properties and comprehensive spectroscopic data analysis.Compounds 1−5 and 7−8 exhibited potent inhibition of lipopolysaccharide(LPS)-induced nuclear factor-κB(NF-κB)with the IC50 values ranging from 6.5 to 21.8μmol L^(−1).In addition,the most potent one,pyrazinemethanol(8),dose-dependently suppressed receptor activator of NF-κB ligand(RANKL)-induced osteoclast differentiation without obvious cytotoxicity in bone marrow macrophages cells(BMMCs),suggesting it is a promising lead compound for the treatment of osteolytic diseases.

Chemistry,Biosynthesis,and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery.The unique marine environment brings us a large group of halogen-containing natural products with abundant biological functionality and good drugability.Meanwhile,biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds.Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years,it is necessary to summarize these compounds with their diverse structures and promising bioactivities.In this review,we have summarized the chemistry,biosynthesis(related halogenases),and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021.Those reviewed chlorinated and brominated compounds with the ratio of 9:1 were predominantly originated from 36 genera of fungi(62%)and 9 bacterial strains(38%)with cytotoxic,antibacterial,and enzyme inhibitory activities,structural types of which are polyketides(38%),alkaloids(27%),phenols(11%),and others.This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.

A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer

Modulating Tankyrases(TNKS),interactions with USP25 to promote TNKS degradation,rather than inhibiting their enzymatic activities,is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway.Here,we identified UAT-B,a novel neoantimycin analog isolated from Streptomyces conglobatus,as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction(PPI)to overcome multi-drug resistance in colorectal cancer(CRC).The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels,triggering cell apoptosis through modulation of the Wnt/β-catenin pathway.Importantly,UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels,as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts,as well as APC^(min/+)spontaneous CRC models.Collectively,these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment,and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

EmbB and EmbC regulate the sensitivity of Mycobacterium abscessus to echinomycin

Treatment of Mycobacterium abscessus(Mab)infections is very challenging due to its intrinsic resistance to most available drugs.Therefore,it is crucial to discover novel anti-Mab drugs.In this study,we explored an intrinsic resistance mechanism through which Mab resists echinomycin(ECH).ECH showed activity against Mab at a minimum inhibitory concentration(MIC)of 2μg/ml.A embC strain in which the embC gene was knocked out showed hypersensitivity to ECH(MIC:0.0078-0.0156μg/ml).The MICs of ECH-resistant strains screened with reference to AembC ranged from 0.25 to 1μg/ml.Mutations in EmbB,including D306A,D306N,R350G,V555l,and G581S,increased the Mab's resistance to ECH when overexpressed in AembC individually(MIC:0.25-0.5μg/ml).These EmbB mutants,edited using the CRISPR/Cpf1 system,showed heightened resistance to ECH(MIC:0.25-0.5μg/ml).The permeability of these Mab strains with edited genes and overexpression was reduced,as evidenced by an ethidium bromide accumulation assay,but it remained significantly higher than that of the parent Mab.In summary,our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH.Mutation in EmbB may partially compensate foralossof EmbCfunction.

Spectroscopy Investigation on Conformational Transition of Tea Glycoconjugate from Green Tea

The conformational transition of a new glycoconjugate, tea glycoconjugate (TGC), was investigated by spec-troscopy techniques including circular dichroism (CD) and ultraviolet (UV) spectroscopy. The solution behaviors of TGC in the mediums of different temperature, pH value, and ions were compared. Results showed that the native conformation of TGC was partially ordered. The CD value and UV absorbance of TGC altered with the change of pH value, temperature, the addition of ions, and also accompanied order-disorder transition. Especially the condi-tions with temperature higher than the glass transition temperature (Tg=62 ℃), higher pH value or lower pH value will have the most impact on the conformation of TGC, which will destroy the hydrogen bonds between the TGC molecules. The results indicated that the outside factors play important roles on the stability of the conformation of TGC.

Semi-synthesis of Several Stigmasterol Saponins

Several stigamasterol saponins were concisely synthesized. Name!y, four monosaccharide （glucopyranose, galactopyranose, xylopyranose, 2-acetamido-2-deoxy-a-D-glucopyranose）, lactopyranose and chacotriose were coupled with 3-OH of stigmasterol. All the compounds were identified by NMR, IR and high resolusion MS.

Synthesis of Two Natural Oleanolic Acid Saponins

3-O-[β-D-Glucopyranosyl-（1→3）-α-L-arabinopyranosyl]-oleanolic acid-28-O-[β-D-glucopyranosyl] ester 1 was synthesized concisely by a convergent strategy. Using stepwise fashion for the synthesis of saponin 2, 3-O-{[β-D-glucopyranosyl-（1→2）]-[α-L-arabinopyranosyl-（1→3）]-α-L-arabinopyranosyl）-oleanolic acid-28-O-（β- D-glucopyranosyl） ester, an abnormal phenomenon, that the terminal arabinosyl residue took the ^1C4 conformation instead of typical ^4C1 form, was observed. Deprotection or heating could not resume the normal conformation, which resulted in the product of 2＇ not 2.

Synthesis of an Ursolic Acid Saponin with N-Acetylglucosamine-containing Trisaccharide Residue

The focus of this work is the synthesis of an ursolic acid saponin with an N-acetylglucosamine-containing trisaccharide residue. Therefore, ursolic acid 3-yl α-L-arabinopyranosyl-（1→2）-α-L-arabinopyranosyl-（1→6）-2- acetamido-2-deoxy-β-D-glucopyranoside （1） was concisely synthesized in convergent synthesis with 48.0% overall yield. The structure of saponin 1 was confirmed by ^1H NMR, ^13C NMR and mass spectra.

Synthesis of Glutamic Acid-based Cluster Galactosides and Their Binding Affinities with Liver Cells

Structurally well defined di-, tri- and tetra-valent cluster galactosides were synthesized in a convenient way. Oligo-glutamic acids were assembled as scaffolds. The presence of amine groups in these three ligands is expected to couple with drugs or genes for delivery. The binding affinities of these cluster galactoses to liver cells were de-termined by in vitro binding studies. Among them, the tetravalent cluster galactose (19) showed the highest affinity to liver cell. It is therefore a promising targeting device for the specific delivery of drugs or genes to parenchymal liver cells.