Wenhan Lin

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Organization: Peking University
Department: State Key Laboratory of Natural and Biomimetic Drugs
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Co-reporter:Yong Li;Dong Liu;Zhongbin Cheng;Peter Proksch
RSC Advances (2011-Present) 2017 vol. 7(Issue 12) pp:7259-7267
Publication Date(Web):2017/01/20
DOI:10.1039/C6RA26956G
Bioassay-guided fractionation of the sponge (Niphates recondite)-associated fungus Stachybotrys chartarum revealed that the EtOAc fraction shows inhibitory effects against tumor cell lines. Chromatographic separation of the active fraction resulted in the isolation of 15 trichothecene-based sesquiterpenes, including four new compounds, namely chartarenes A–D (1–4). The structures of the new compounds were determined on the basis of extensive spectroscopic analysis and chemical conversion. Compounds 1–15 exerted potent or selective inhibition against a panel of tumor cell lines including HCT-116, HepG2, BGC-823, NCI-H1650, and A2780, with IC50 values ranging from 10−2 to 10 μM. In addition, these compounds showed potent inhibition against tumor-related kinases FGFR3, IGF1R, PDGFRb, and TRKB.
Co-reporter:Wei Cheng, Zhen Liu, Yang Yu, Leen van Ofwegen, Peter Proksch, Siwang Yu, Wenhan Lin
Bioorganic & Medicinal Chemistry Letters 2017 Volume 27, Issue 12(Issue 12) pp:
Publication Date(Web):15 June 2017
DOI:10.1016/j.bmcl.2017.04.058
•Scleronine presents as a pregnane-bearing unprecedented scaffold.•A total synthesis of dehydroscleronine is achieved.•Both compounds inhibit the migration of tumor cells.•Mechanism relates to down-regulation of TGFβ, TNFα, IL-1β, and IL-6 genes.An unprecedented spinaceamine-bearing pregnane namely scleronine (1) was isolated from a Chinese soft coral Scleronephthya sp. Its structure was determined on the basis of 1D and 2D NMR spectroscopic analyses in association with the HRESIMS data, while the absolute configurations were deduced by the single-crystal X-ray diffraction analysis. In addition, a dehydrogenated analogue (3) was synthesized through six steps with pregna-1,20-dien-3-one (2) as a precursor. The significantly inhibitory effects of 1 and 3 against the migration of tumor cells A549 and B16 accompanying the down-regulation of key genes (TGFβ, TNFα, IL-1β, and IL-6) were observed. These findings suggested that both 1 and 3 are potential for therapeutic usage aiming at cancer metastasis inhibition.Download high-res image (157KB)Download full-size image
Co-reporter:Siwen Niu, Dong Liu, Zongze Shao, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2017 Volume 58, Issue 38(Issue 38) pp:
Publication Date(Web):20 September 2017
DOI:10.1016/j.tetlet.2017.08.015
•Eutypellazines N-S are discovered from Eutypella sp. as new alkaloids.•Eutypellazines N-P with spirocyclic skeletons are rarely found from nature.•Eutypellazines P-R inhibited vancomycin-resistant enterococci.Chemical investigation of a deep sea sediment derived fungus Eutypella sp. MCCC 3A00281 resulted in the isolation of six new thiodiketopiperazine alkaloids, namely eutypellazines N-S (1−6). Their structures were elucidated on the basis of the extensive NMR and mass spectroscopic analysis, including the ECD data for the determination of absolute configuration. The structures of eutypellazines N-P (1−3) were characteristic of unique spirocyclic skeletons, while eutypellazines N-O bearing a spirocyclic tetrahydrobenzothiophene motif were found from wide type fungus for the first time. The biogenetic generation of the spirocyclic skeletons was postulated. Compounds 3–5 exhibited inhibitory effects against vancomycin-resistant enterococci (VRE), suggesting that they may be the potential inhibitors toward drug resistant pathogenic bacteria after the structural modification.Download high-res image (84KB)Download full-size image
Co-reporter:Dong Liu, Yong Li, Xiaodan Li, Zhongbin Cheng, Jian Huang, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2017 Volume 58, Issue 19(Issue 19) pp:
Publication Date(Web):10 May 2017
DOI:10.1016/j.tetlet.2017.03.079
•Chartarolides A-B present as new scaffold with unprecedented meroterpenoid.•Chartarolides A-C significantly inhibit a panel of tumor cell lines.•FGFR3, IGF1R, PDGFRb, and TrKB kinases play key role for the antitumor effects.Three phenylspirodrimane-based meroterpenoids with novel scaffolds, namely chartarolides A-C (1–3), were isolated from a sponge (Niphates recondite) associated fungus Stachybotrys chartarum WGC-25C-6. Their structures were determined on the basis of comprehensive analyses of the spectroscopic data (IR, 1D and 2D NMR, HRESIMS), including the TDDFT-ECD calculation for the assignments of absolute configurations. The biogenetic generation of 1–3 through the conjunction of phenylspirodrimane and mollicellin-type analogues as the precursors was postulated. Chartarolides A-C exhibited significant cytotoxic activities against a panel of human tumor cell lines, and showed strong inhibitory activities against the human tumor related protein kinases of FGFR3, IGF1R, PDGFRb, and TrKB.Download high-res image (152KB)Download full-size image
Co-reporter:Wei Cheng, Ming Ji, Xiaodan Li, Jinwei Ren, Fuling Yin, Leen van Ofwegen, Siwang Yu, Xiaoguang Chen, Wenhan Lin
Tetrahedron 2017 Volume 73, Issue 17(Issue 17) pp:
Publication Date(Web):27 April 2017
DOI:10.1016/j.tet.2017.03.037
Chemical investigation of the gorgonian coral Junceella fragilis resulted in the isolation of a new norditerpenoid fragilolide A (1), sixteen new briarane diterpenoids fragilolides B-Q (2–17), together with frajunolides H and N, and three known norcembranoids scabrolide D, sinuleptolide and 5-epi-sinuleptolide. The structures of new compounds were determined on the basis of extensive spectroscopic analysis, including the experimental and calculated ECD data and single-crystal X-ray diffraction for the configurational assignments. The structure of fragilolide A featured an unprecedented 4,13- and 7,11-fused tetracyclic norcembranoid, while the biogenetic relationships of the briarane analogues were postulated. Frajunolide H exerted significant inhibition against a panel of tumor cell lines, and six briarane diterpenoids (3, 6, 8, 12, 16, and frajunolide N) exhibited the inhibitory effects against the HBeAg express of hepatitis B virus in HepAD38 cells. In addition, sinuleptolide and 5-epi-sinuleptolide exerted the effects to inhibit NO production in RAW264.7 macrophage cells, in addition to the activation of ARE and the inhibition of NF-κB expression.Download high-res image (333KB)Download full-size image
Co-reporter:Ran Chen;Zhongbin Cheng;Jian Huang;Dong Liu;Chongming Wu;Peng Guo
RSC Advances (2011-Present) 2017 vol. 7(Issue 78) pp:49235-49243
Publication Date(Web):2017/10/20
DOI:10.1039/C7RA07940K
Lipid-lowering assay guided fractionation of a gorgonian-derived fungus Aspergillus versicolor LZD-14-1 resulted in the isolation of three new cyclopeptides namely versicotides D–F (1–3) and the known analogues versicotides A and B. The new structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS), while the data of the X-ray crystallography and Marfey's method were used for the configurational assignment. Versicotides E–F (2–3) are characterized by the presence of two anthranilic acid residues and a proline that coexisted in the cyclic pentapeptides, which are rarely found from nature. Versicotides D–F (1–3) exerted lipid-lowering effects through the regulation of cholesterol efflux to HDL in RAW264.7 macrophages. The mechanistic study revealed that the cholesterol efflux and influx induced by the peptides are directly related to the promotion of the target genes ABCG1 and LXRα, in addition to the decreasing critical scavenger receptors CD36 and SR-1/SR-2. The present work provided a group of new cyclopeptides which are promising for the development of anti-atherosclerosis leads.
Co-reporter:Siwen Niu;Dong Liu;Zongze Shao;Peter Proksch
RSC Advances (2011-Present) 2017 vol. 7(Issue 53) pp:33580-33590
Publication Date(Web):2017/06/29
DOI:10.1039/C7RA05774A
Bioassay in association with the NMR/MS spectroscopic data guided fractionation of the solid fermentation of a deep sea derived fungus Eutypella sp. MCCC 3A00281, resulted in the isolation of 13 new thiodiketopiperazine-type alkaloids, namely eutypellazines A–M (1–13). Their structures were elucidated on the basis of extensive spectroscopic data analysis, including the ECD data, modified Mosher's method, and the Cu-Kα X-ray single-crystal diffraction experiments for the determination of the absolute configurations. An anti-HIV bioassay indicated that compounds 1–12 exhibited inhibitory effects against pNL4.3.Env-.Luc co-transfected 293T cells (HIV-1 model cells) with low cytotoxicity, of which eutypellazine E exerted the highest activity. A preliminary structure–activity relationship was discussed. In addition, eutypellazine J (10) and epicoccin A showed reactivating effects toward latent HIV-1 in J-Lat A2 cells.
Co-reporter:Hailin Long, Zhongbin Cheng, Wei Huang, Qi Wu, Xiaodan Li, Jingrong Cui, Peter Proksch, and Wenhan Lin
Organic Letters 2016 Volume 18(Issue 18) pp:4678-4681
Publication Date(Web):August 29, 2016
DOI:10.1021/acs.orglett.6b02313
Three novel asteltoxin-bearing dimers namely diasteltoxins A–C (1–3) along with asteltoxin were isolated from a mutated strain of a sponge-derived fungus Emericella variecolor XSA-07-2. Their structures were determined by extensive spectroscopic analyses including the computed electronic circular dichroism (ECD) data for the configurational assignment. The biogenetic formation of the dimers through [2 + 2] cycloaddition of asteltoxin was postulated. Diasteltoxins 1–3 exerted inhibitory effects against the tumor cell lines H1299 and MCF7 and exhibited significant inhibition against thioredoxin reductase (TrxR).
Co-reporter:Siwen Niu, Longlong Si, Dong Liu, Andrew Zhou, Ziwei Zhang, Zongze Shao, Shaomeng Wang, Lihe Zhang, Demin Zhou, Wenhan Lin
European Journal of Medicinal Chemistry 2016 Volume 108() pp:229-244
Publication Date(Web):27 January 2016
DOI:10.1016/j.ejmech.2015.09.037
•Spiromastilactone A-M were isolated as new polyketides from a deep-sea fungus Spiromastix sp.•Spiromastilactone D exerted potent inhibitory activity against WSN influenza virus.•Spiromastilactone D inhibited a panel of drug resistant clinical isolates.•Spiromastilactone D synergistically targeted hemagglutinin and RNP complexes to disrupt the viral entry and replication.A new class of phenolic lactones with trivial names of spiromastilactones A-M (1–13) was isolated from a deep-sea derived Spiromastix sp. fungus. Their structures featured by various chlorination at aromatic rings were determined on the basis of extensive spectroscopic analyses. An antiviral assay revealed that most of the tested compounds exert inhibitory activity against WSN influenza virus with low cytotoxicity, while the structure–activity relationships were discussed. Spiromastilactone D (4), a 5′-chloro-2′-methoxy substituted analogue, displayed the most potent to inhibit a panel of influenza A and B viruses in addition to drug-resistant clinical isolates. Mechanistic investigation resulted in that compound 4 bonded to hemagglutinin protein (HA), potentially at the spherical head, and disrupted the HA-sialic acid receptor interaction, that is essential for the attachment and entry of all influenza viruses. In addition, compound 4 also showed inhibitory effect toward viral genome replication via targeting viral RNP complex. The synergistic effects of 4 on both viral entry and replication assumed it to be a promising lead for the development of a new influenza inhibitor.Spiromastilactone D exerted synergistic inhibition on viral entry and replication of WSN influenza virus by synergistically targeting hemagglutinin and RNP complexes.
Co-reporter:Zhongbin Cheng, Lanlan Lou, Dong Liu, Xiaodan Li, Peter Proksch, Sheng Yin, and Wenhan Lin
Journal of Natural Products 2016 Volume 79(Issue 11) pp:2941-2952
Publication Date(Web):November 10, 2016
DOI:10.1021/acs.jnatprod.6b00801
Eleven fumiquinazoline-type alkaloids, namely, versiquinazolines A–K (1–11), along with cottoquinazolines B–D, were isolated from the gorgonian-derived fungus Aspergillus versicolor LZD-14-1. Their structures were determined by extensive analyses of the spectroscopic data (1D and 2D NMR, HRESIMS), in addition to the experimental and calculated ECD data and X-ray single-crystal diffraction analysis for the assignments of the absolute configurations. Versiquinazolines A, B, and F (1, 2, and 6), bearing a methanediamine or an aminomethanol unit and representing a unique subtype of fumiquinazolines, were found from nature for the first time. Possible biogenetic relationships of the versiquinazolines are postulated. In addition, the structures of cottoquinazolines B (12), D (13), and C (14) should be revised to the enantiomers. Compounds 1, 2, 7, and 11 exhibited inhibitory activities against thioredoxin reductase (IC50 values ranging from 12 to 20 μM).
Co-reporter:Zhongbin Cheng; Jingjun Zhao; Dong Liu; Peter Proksch; Zhimin Zhao
Journal of Natural Products 2016 Volume 79(Issue 4) pp:1035-1047
Publication Date(Web):February 29, 2016
DOI:10.1021/acs.jnatprod.5b01103
Chemical examination of an EtOAc extract of a cultured Acremonium sp. fungus from deep-sea sediments resulted in the isolation of 15 new eremophilane-type sesquiterpenoids, namely, acremeremophilanes A–O (1–15), together with seven known analogues. The structures of new compounds were determined through extensive spectroscopic analyses, in association with chemical conversions and ECD calculations for configurational assignments. The PKS-derived 4-hexenoic acid unit in 2–6 is rarely found in nature. All compounds were evaluated for inhibitory effects toward nitric oxide production induced by lipopolysaccharide in RAW 264.7 macrophage cells. Compounds 2–6 and 14 exhibited inhibitory effects with IC50 values ranging from 8 to 45 μM.
Co-reporter:Chongming Wu, Yang Zhao, Ran Chen, Dong Liu, Mingyue Liu, Peter Proksch, Peng Guo and Wenhan Lin  
RSC Advances 2016 vol. 6(Issue 26) pp:21969-21978
Publication Date(Web):17 Feb 2016
DOI:10.1039/C6RA00033A
Chemical examination of the mangrove-associated fungus Penicillium pinophilum (H608) resulted in the isolation of 16 phenolic metabolites, including a new metabolite, namely 5′-hydroxypenicillide (1). The structure of the new compound was determined by extensive spectroscopic analyses, in association with the Mosher method for configurational assignment. All compounds were tested for inhibitory effects against oleic acid (OA)-elicited lipid accumulation in HepG2 cells, while eight compounds (4, 7–8, and 11–15) exhibited inhibition toward lipid accumulation at a dose of 10 μM with no cytotoxic effect. Further investigation revealed six compounds (4, and 11–15) that significantly suppressed intracellular total cholesterol (TC) and triglycerides (TGs). A real-time quantitative PCR indicated that compounds 4, 11, and 13–15 dramatically decreased the expression of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in association with up-regulation of carnitinepalmitoyl transferase-1 (CPT-1). In addition, seven compounds (4, 8, 11, and 13–16) significantly reduced oxidized low-density lipoprotein stimulated lipid accumulation in RAW264.7 cells. Mechanistic study revealed that compounds 14–16 remarkably decreased CD36 and SR-1 transcription, while compounds 4 and 15 dramatically up-regulated PPARγ, LXRα and ABCG1 to promote cholesterol efflux. This work provided a group of new chemical entities as promising leads for the development of hypolipidemic and anti-atherosclerotic agents.
Co-reporter:Jingyuan Sun, Wei Cheng, Nicole J. de Voogd, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2016 Volume 57(Issue 38) pp:4288-4292
Publication Date(Web):21 September 2016
DOI:10.1016/j.tetlet.2016.08.024
•Three new cycloheptapeptides were isolated from sponge Stylissa massa.•New structures were determined by spectroscopic analyses and Marfey’s method.•Stylissatin B exhibited inhibition against a panel of tumor cell lines.The NMR and LC–MS guided chromatographic fractionation of the CH2Cl2 extract of the sponge Stylissa massa resulted in the isolation of three new cycloheptapeptides, namely stylissatins B–D (1–3), together with ten known cyclopeptides. The structures of stylissatins B–D were established by comprehensive analysis of 2D NMR (COSY, TOCSY, HMQC, HMBC, and ROESY) in association with the ESI-MS/MS fragmentation. The L-configuration of the amino acid residues was determined based on the Marfey’s method. Stylissatin B (1) exhibited the inhibitory effects against a panel of human tumor cell lines including HCT-116, HepG2, BGC-823, NCI-H1650, A2780, and MCF7 with the IC50 values ranging from 2.4 to 9.8 μM.
Co-reporter:Zhongbin Cheng;Dong Liu;Nicole J. de Voogd;Peter Proksch
Helvetica Chimica Acta 2016 Volume 99( Issue 8) pp:588-596
Publication Date(Web):
DOI:10.1002/hlca.201600021

Chemical examination of a marine sponge Xestospongia sp. resulted in the isolation of 20 sterol derivatives (120), including eight new sterols namely aragusterols J – L (13), (5α,7α,12β,22E)-7,12,18-trihydroxystigmast-22-en-3-one (4), (5α,7α,12β,24R)- and (5α,7α,12β,24S)-7,12,20-trihydroxystigmastan-3-one (5/6), and (5α,7α,12β,22E,24R)- and (5α,7α,12β,22E,24S)-7,12,20-trihydroxyergost-22-en-3-one (7/8). The structures of new compounds were determined through extensive spectroscopic analyses and chemical conversion. The sterol diversity was mainly characterized by the presence of a cyclopropane unit at side chain, while compound 4 with 18-hydroxymethyl group was found in stigmasterol family for the first time. Cytotoxic test revealed the inhibitory effects of compounds 1, 4, and 17 against human leukemia cell line K562 with IC50 values of 18.3, 24.1, and 34.3 μm, respectively.

Co-reporter:Zehong Wu, Yongrui Wang, Dong Liu, Peter Proksch, Siwang Yu, Wenhan Lin
Tetrahedron 2016 Volume 72(Issue 1) pp:50-57
Publication Date(Web):7 January 2016
DOI:10.1016/j.tet.2015.10.038
Bioassay-guided fractionation and chromatographic separation of a deep-sea fungus Aspergillus versicolor resulted in the isolation of 22 phenolic compounds, of which six were new natural products namely aspergilols A–F (1–6). The structures of the new compounds were determined through extensive spectroscopic analysis, including the ECD data and chemical conversion for the configurational assignment. Aspergilols A and B presented as a new scaffold with a C–C fusion of an anthraquinone and orcinol unit. The trolox equivalent antioxidant capacity (TEAC) assay indicated most of the phenolic compounds possessing antioxidant activities, while four compounds (12, 14, 21, and 22) exerted strong free-radical scavenging effects with the TEAC values around five folds more than trolox. In addition, an Nrf2-dependent luciferase reporter gene assay revealed that compounds 12–14 and 17–18 potentially activated the expression of Nrf2-regulated gene. The primary structure–activity relationship was discussed. These findings provided the evidence that the deep-sea derived microorganisms are the promising and new source for the discovery of antioxidant agents.
Co-reporter:Dong Liu, Hong Lin, Peter Proksch, Xixiang Tang, Zhongze Shao, and Wenhan Lin
Organic Letters 2015 Volume 17(Issue 5) pp:1220-1223
Publication Date(Web):February 12, 2015
DOI:10.1021/acs.orglett.5b00172
Two new peptaibols, namely microbacterins A (1) and B (2), were isolated from the deep sea inhabited actinomycete Microbacterium sediminis spp. nov. YLB-01(T). The sequences of the amino acid residues were determined on the basis of intensive NMR and ESI-MS/MS spectroscopic analysis, in addition to the Marfey’s method and CD and optical rotation data for the configurational assignment. Both 1 and 2 exhibited significant cytotoxic activities against a panel of human tumor cell lines.
Co-reporter:Qi Wu; Chongming Wu; Hailin Long; Ran Chen; Dong Liu; Peter Proksch; Peng Guo
Journal of Natural Products 2015 Volume 78(Issue 10) pp:2461-2470
Publication Date(Web):September 22, 2015
DOI:10.1021/acs.jnatprod.5b00578
Chemical examination of a sponge (Cinachyrella sp.)-associated Emericella variecolor fungus resulted in the isolation of seven new polyketide derivatives, namely, varioxiranols A–G (1–7), and a new hybrid PKS-isoprenoid metabolite, 19-O-methyl-22-methoxypre-shamixanthone (8), together with nine known analogues. Their structures were elucidated on the basis of extensive spectroscopic analyses, including ECD effects, Mosher’s method, X-ray diffraction, and chemical conversion for the determination of absolute configurations. Varioxiranols F and G were found for the first time to link a xanthone moiety with a benzyl alcohol via an ether bond, while the dioxolanone group of 5 is unusual in nature. A cell-based lipid-lowering assay revealed that pre-shamixanthone (12) exerted significant inhibition against lipid accumulation in HepG2 cells without cytotoxic effects, accompanying the potent reduction of total cholesterol and triglycerides. Real-time quantitative PCR indicated that pre-shamixanthone (12) mediated the reduction of lipid accumulation related to the down-regulation of the expression of the key lipogenic transcriptional factor SREBP-1c and its downstream genes encoding FAS and ACC.
Co-reporter:Xueqing Chen, Longlong Si, Dong Liu, Peter Proksch, Lihe Zhang, Demin Zhou, Wenhan Lin
European Journal of Medicinal Chemistry 2015 Volume 93() pp:182-195
Publication Date(Web):26 March 2015
DOI:10.1016/j.ejmech.2015.02.006
•Rubrumlines A–O were isolated as new alkaloids from fungus Eurotium rubrum.•Neoechinulin B exerted potent inhibition against H1N1 virus infected in MDCK cells.•Neoechinulin B inhibited a panel of drug resistant clinical isolates.•Neoechinulin B targeted at hemagglutinin to disrupt the interaction of HA with the sialic acid receptor.A class of prenylated indole diketopiperazine alkaloids including 15 new compounds namely rubrumlines A-O obtained from marine-derived fungus Eurotium rubrum, were tested against influenza A/WSN/33 virus. Neoechinulin B (18) exerted potent inhibition against H1N1 virus infected in MDCK cells, and is able to inhibit a panel of influenza virus strains including amantadine- and oseltamivir-resistant clinical isolates. Mechanism of action studies indicated that neoechinulin B binds to influenza envelope hemagglutinin, disrupting its interaction with the sialic acid receptor and the attachment of viruses to host cells. In addition, neoechinulin B was still efficient in inhibiting influenza A/WSN/33 virus propagation even after a fifth passage. The high potency and broad-spectrum activities against influenza viruses with less drug resistance make neoechinulin B as a new lead for the development of potential inhibitor of influenza viruses.Neoechinulin B exerted potent inhibition against H1N1 virus infected in MDCK cells and the drug-resistant clinical isolates by targeting hemagglutinin to disrupt the interaction of HA with the sialic acid receptor.
Co-reporter:Yang Zhao, Longlong Si, Dong Liu, Peter Proksch, Demin Zhou, Wenhan Lin
Tetrahedron 2015 Volume 71(Issue 18) pp:2708-2718
Publication Date(Web):6 May 2015
DOI:10.1016/j.tet.2015.03.033
Fourteen new isoprenylated cyclohexanols namely truncateols A–N (1–14) were isolated from the solid culture of the sponge-associated fungus Truncatella angustata. Their structures were determined on the basis of extensive spectroscopic analyses, including the modified Mosher's method and ECD, as well as X-ray diffraction for the assignment of absolute configurations. The structures of truncateols are characterized by the presence of unique alkynyl or allenyl groups. Truncateol M (13) exerted potent inhibitory effect against influenza-A viral infection by targeting virion assembly/release step.
Co-reporter:Yong Li, Chongming Wu, Dong Liu, Peter Proksch, Peng Guo, and Wenhan Lin
Journal of Natural Products 2014 Volume 77(Issue 1) pp:138-147
Publication Date(Web):January 3, 2014
DOI:10.1021/np400824u
Chemical examination of the solid culture of the endophytic fungus Stachybotrys chartarum isolated from the sponge Niphates recondita resulted in the isolation of 16 new phenylspirodrimanes, named chartarlactams A–P (1–16), together with eight known analogues. Their structures were determined on the basis of extensive spectroscopic analysis, including X-ray single-crystal diffraction for the determination of the absolute configurations. The isoindolone-drimane dimer chartarlactam L (12) was determined as a new skeleton. Compounds 1–6 and 8–24 were evaluated for antihyperlipidemic effects in HepG2 cells, and the primary structure–activity relationships are discussed.
Co-reporter:Siwen Niu ; Dong Liu ; Xinxin Hu ; Peter Proksch ; Zhongzhe Shao
Journal of Natural Products 2014 Volume 77(Issue 4) pp:1021-1030
Publication Date(Web):February 26, 2014
DOI:10.1021/np5000457
Fifteen new depsidone-based analogues named spiromastixones A–O (1–15) were isolated from the fermentation broth of a deep-sea Spiromastix sp. fungus. Their structures were elucidated on the basis of extensive NMR and mass spectroscopic analysis in association with chemical conversion. Spiromastixones A–O are classified into two subtypes based on the orientation of ring C relative to ring A, while the n-propyl substituents on rings A and C are rarely seen in natural products. Most analogues are substituted by various numbers of chlorine atoms. All compounds exhibited significant inhibition against Gram-positive bacteria including Staphylococcus aureus, Bacillus thuringiensis, and Bacillus subtilis with MIC values ranging from 0.125 to 8.0 μg/mL. In addition, compounds 6–10 displayed potent inhibitory effects against methicillin-resistant bacterial strains of S. aureus (MRSA) and S. epidermidis (MRSE), while 10 also inhibited the growth of the vancomycin-resistant bacteria Enterococcus faecalis and E. faecium (VRE). The structure–activity relationships are discussed.
Co-reporter:Dawei Chen, Wei Cheng, Dong Liu, Leen van Ofwegen, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2014 Volume 55(Issue 19) pp:3077-3082
Publication Date(Web):7 May 2014
DOI:10.1016/j.tetlet.2014.03.132
Chemical examination of the soft coral Sinularia capillosa resulted in the isolation of eight new sesquiterpenoids named capillosananes S–Z (1–8) and six known sesquiterpenes. The structures of the new compounds were determined on the basis of extensive spectroscopic analysis, including CD effects and Mosher method for the assignment of their absolute configurations. Capillosananes S–U (1–3) presented as the novel carbon skeletons with bicyclo[3,6,0] and bicyclo[4,5,0] systems, while capillosanane V (4) was characteristic of an unprecedented tricyclic skeleton. Capillosananes W–X (5–6) were assigned to the unusual dumortane-type sesquiterpenes. In addition, the absolute configurations of the stereoisomers of isodaucene-9,14-diol were assigned for the first time.
Co-reporter:Dong Liu, Aigang Yang, Chongming Wu, Peng Guo, Peter Proksch, Wenhan Lin
Bioorganic & Medicinal Chemistry Letters 2014 Volume 24(Issue 22) pp:5288-5293
Publication Date(Web):15 November 2014
DOI:10.1016/j.bmcl.2014.09.049
Bioassay-guided fractionation of the fermentation broth of Arctic Streptomyces nitrosporeus YBH10-5 resulted in the isolation of seven new compounds named nitrosporeunols A–G (1–7), together with seven known analogues (8–14). Their structures were determined based on extensive spectroscopic analysis. Compounds 1–14 were evaluated for the lowering lipid effects, while two compounds (10 and 12) remarkably decreased lipid levels including total cholesterol (TC) and triglycerides (TG) in HepG2 cells. Quantitative realtime PCR and Western blot indicated that farnesylquinone (12) increased the expression of the key proteins including peroxisome proliferator-activated receptor-α (PPARα), peroxisome proliferator-activated receptor-γ, and coactivator 1α (PGC-1α), as well as their downstream genes carnitine palmitoyltransterase-1 (CPT-1), acyl-coenzyme A oxidase 1 (ACOX), malonyl CoA decarboxylase 1 (MCD1), pyruvate dehydrogenase kinase 4 (PDK4), and cholesterol 7α -hydroxylase (CYP7A1). Luciferase assay showed that 12 increased the transcriptional activity of PPARα, while its lipid-lowering effect was abolished by PPARα inhibitor, MK886, in HepG2 cells. These findings suggested that 12 is a potent lipid-lowering agent which may decrease lipid levels through upregulation of PPARα pathway.
Co-reporter:Jian Bai, Dong Liu, Siwang Yu, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2014 Volume 55(Issue 45) pp:6286-6291
Publication Date(Web):5 November 2014
DOI:10.1016/j.tetlet.2014.09.100
Chemical examination of the fermentation broth of the marine-derived bacterium Bacillus sp. resulted in the isolation of seven new amicoumacin-type isocoumarin derivatives, namely bacillcoumacins A–G (1–7), together with four known analogues. Their structures were elucidated on the basis of extensive spectroscopic analysis, while the absolute configurations of the new compounds were determined by CD, Mosher’s method, and chemical conversion. Compounds 7 and 9 showed inhibitory effects against the NO production induced by lipopolysaccharide (LPS) in mouse macrophage RAW 264.7 cells.
Co-reporter:Zhen Liu, Wei Cheng, Dong Liu, Leen van Ofwegen, Peter Proksch, Wenhan Lin
Tetrahedron 2014 70(45) pp: 8703-8713
Publication Date(Web):
DOI:10.1016/j.tet.2014.09.034
Co-reporter:Yong Li, Dong Liu, Shan Cen, Peter Proksch, Wenhan Lin
Tetrahedron 2014 70(39) pp: 7010-7015
Publication Date(Web):
DOI:10.1016/j.tet.2014.07.047
Co-reporter:Yao Wang, Xixiang Tang, Zhongzhe Shao, Jinwei Ren, Dong Liu, Peter Proksch and Wenhan Lin
The Journal of Antibiotics 2014 67(5) pp:395-399
Publication Date(Web):February 5, 2014
DOI:10.1038/ja.2014.3
Chromatographic separation of a crude extract obtained from a fermentation broth of a chemically unknown bacterium Shewanella piezotolerans WP3 collected in deep-sea yielded three new indole alkaloids namely shewanellines A (1a), B (1b) and C (2), together with 12 known indole alkaloids. The structures were unambiguously elucidated on the basis of 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC and NOESY) in association with MS and CD data. Compounds 1–4, 7, 9 and 11–14 were selected for the evaluation of their cytotoxic activities against human tumor cell lines HL-60 and BEL-7402, whereas compounds 2, 4 and 9 exhibited significant inhibition toward HL-60.
Co-reporter:Wei Cheng, Dong Liu, Fengying Zhang, Qingying Zhang, Patchara Pedpradab, Peter Proksch, Hong Liang, Wenhan Lin
Tetrahedron 2014 70(22) pp: 3576-3583
Publication Date(Web):
DOI:10.1016/j.tet.2014.04.008
Co-reporter:Aigang Yang, Longlong Si, Zhenping Shi, Li Tian, Dong Liu, Demin Zhou, Peter Proksch, and Wenhan Lin
Organic Letters 2013 Volume 15(Issue 20) pp:5366-5369
Publication Date(Web):October 3, 2013
DOI:10.1021/ol4026809
Chemical examination of an arctic actinomycete Streptomyces nitrosporeus resulted in the isolation of two new alkaloids named nitrosporeusines A (1) and B (2), an unprecedented skeleton containing benzenecarbothioc cyclopenta[c]pyrrole-1,3-dione. Their structures were determined through extensive spectroscopic analyses in association with X-ray single crystal diffraction. Both 1 and 2 exhibited inhibitory activities against the H1N1 virus in MDCK cells.
Co-reporter:Dawei Chen, Wei Chen, Dong Liu, Leen van Ofwegen, Peter Proksch, and Wenhan Lin
Journal of Natural Products 2013 Volume 76(Issue 9) pp:1753-1763
Publication Date(Web):August 21, 2013
DOI:10.1021/np400480p
Chemical examination of the soft coral Sinularia capillosa collected from the South China Sea resulted in the isolation of 14 new asteriscane-type sesquiterpenoids, namely, capillosananes A–N (1–14), four new seco-asteriscanes, capillosananes O–R (15–18), and (−)-sinularone A and sinularone A. Their structures were determined on the basis of extensive spectroscopic analyses, while the absolute configurations were determined by CD and ECD calculation, Mosher’s method, and chemical conversion. This is the first report of asteriscane-type sesquiterpenoids from soft corals, and capillosananes Q (17) and R (18) represent new seco-asteriscane skeletons. Capillosanane A exhibited potent antifouling activity against Balanus amphitrite, with an IC50 value of 9.70 μM, while capillosananes B and I and (−)-sinularone A inhibited inflammation-related TNF-α in vitro.
Co-reporter:Jinwei Ren, Yi Yang, Dong Liu, Wei Chen, Peter Proksch, Bing Shao, Wenhan Lin
Journal of Chromatography A 2013 Volume 1309() pp:90-95
Publication Date(Web):27 September 2013
DOI:10.1016/j.chroma.2013.08.026
•A simple and sensitive method was developed for sequencing short peptaibol in a mixture.•Minor and new microheterogeneous peptaibols were detected.•A total of 32 new peptaibols were determined from a marine-derived fungus Trichoderma asperellum.Thirty-eight short peptaibols in a microheterogeneous mixture derived from the fermentation broth of a marine-derived fungus Trichoderma asperellum were determined using ultrahigh pressure liquid chromatography in combination with electrospray-ionization tandem mass spectrometry (UHPLC–ESIMS/MS) techniques, including thirty-two new peptaibols namely asperelines G-Z13. The C-terminus bonded to proline (aspereline Z9) or hydroxyprolinol (aspereline Z12) is rarely found in nature. So far, it is the largest number of peptaibols to be detected at once on the basis of the selected ion monitoring (SIM) mode coupled to precursor scan techniques.
Co-reporter:Daowan Lai, Zhufeng Geng, Zhiwei Deng, Leen van Ofwegen, Peter Proksch, and Wenhan Lin
Journal of Agricultural and Food Chemistry 2013 Volume 61(Issue 19) pp:4585-4592
Publication Date(Web):April 26, 2013
DOI:10.1021/jf401303q
Chemical examination of the soft coral Sinularia rigida resulted in the isolation of 12 new cembranoids, namely, sinulariols T–Z5 (1–12), together with a known analogue, 13. Their structures were determined on the basis of 1D and 2D NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analyses in association with MS and IR data. Compounds 7 and 13 showed potent antifouling activity for the inhibition against the barnacle Balanus amphitrite and moderate inhibition against Bugula neritina. The primary structure–activity relationship is discussed.
Co-reporter:Jinwei Ren, Dong Liu, Li Tian, Yangye Wei, Peter Proksch, Jinzhang Zeng, Wenhan Lin
Bioorganic & Medicinal Chemistry Letters 2013 Volume 23(Issue 1) pp:301-304
Publication Date(Web):1 January 2013
DOI:10.1016/j.bmcl.2012.10.096
Five new phenoxazine-based alkaloids venezuelines A–E (1–5) and two new aminophenols venezuelines F–G (6–7), as well as three known analogues exfoliazone, chandrananimycin D and carboxyexfoliazone were isolated from the fermentation broth of the marine-derived bacterium Streptomyces venezuelae. The structures of new compounds were determined on the basis of extensive spectroscopic analysis. The cytotoxic activity of these compounds against a panel of tumor cell lines were tested, while the regulation of gene target Nur77 of 2 and exfoliazone (8) were evaluated.
Co-reporter:Zhifang Xi;Wei Bie;Wei Chen;Dong Liu;Leen vanOfwegen;Peter Proksch
Helvetica Chimica Acta 2013 Volume 96( Issue 12) pp:2218-2227
Publication Date(Web):
DOI:10.1002/hlca.201300086

Abstract

Six new biscembranoids, namely, sarcophytolides G–L (16, resp.), together with six known analogs, were isolated from a marine soft coral Sarcophyton elegans. The structures of the new compounds were established on the basis of 1D- and 2D-NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analysis together with the aid of MS, CD, and IR data. The unusual isobiscembranoid sarcophytolide G (1) was found for the first time in the genus Sarcophyton.

Co-reporter:Daowan Lai, Dong Liu, Zhiwei Deng, Leen van Ofwegen, Peter Proksch, and Wenhan Lin
Journal of Natural Products 2012 Volume 75(Issue 9) pp:1595-1602
Publication Date(Web):August 20, 2012
DOI:10.1021/np300404f
Twelve new eunicellin-based diterpenoids, astrogorgins B–M (1–12), were isolated from a Chinese gorgonian Astrogorgia sp., together with ophirin, muricellin, astrogorgin, calicophirins A and B, and 14-deacetoxycalicophirin B. The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with data reported in the literature. Significant antifouling activity was observed for 14-deacetoxycalicophirin B against the larval settlement of the barnacle Balanus amphitrite at nontoxic concentrations with an EC50 = 0.59 μg/mL, while the other analogues were effective within an EC50 range of 5.14–17.8 μg/mL.
Co-reporter:Dawei Chen, Shanjiang Yu, Leen van Ofwegen, Peter Proksch, and Wenhan Lin
Journal of Agricultural and Food Chemistry 2012 Volume 60(Issue 1) pp:112-123
Publication Date(Web):December 7, 2011
DOI:10.1021/jf2040862
Fifteen new guaiazulene-based terpenoids designated anthogorgienes A–O (1–15) were isolated from a Chinese gorgonian Anthogorgia sp., together with eight known analogues (16–23). The structural patterns were classified into monomers, dimers, and trimers, which were supposed to be generated from a precursor guaiazulene and followed by side-chain and nucleus oxidation and oxidative rearrangement. The structures of new compounds were elucidated on the basis of extensive spectroscopic (IR, MS, and 1D and 2D NMR) data analysis. A possible biogenetic relationship of the isolated compounds was postulated. Some of the compounds showed potent antifouling activities against the larval settlement of barnacle Balanus amphitrite, whereas their antibiotic activities were also evaluated.
Co-reporter:Yongxin Li, Shanjiang Yu, Dong Liu, Peter Proksch, Wenhan Lin
Bioorganic & Medicinal Chemistry Letters 2012 Volume 22(Issue 2) pp:1099-1102
Publication Date(Web):15 January 2012
DOI:10.1016/j.bmcl.2011.11.109
Four new polyphenols namely excoecariphenols A–D (1–4) were isolated from the Chinese mangrove plant Excoecaria agallocha L. together with 23 known phenolic compounds. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses including IR, MS, NMR, and CD data. Excoecariphenols A and B presented as the unusual flavane-based 1-thioglycosides. Part of the isolated polyphenols were tested against hepatitis C NS3-4A protease and HCV RNA in huh 7.5 cells. Excoecariphenol D, corilagin, geraniin, and chebulagic acid showed potential inhibition toward HCV NS3-4A protease with IC50 values in a range of 3.45–9.03 μM, while excoecariphenol D and corilagin inhibited HCV RNA in huh 7.5 cells significantly. A primary structure–activity relationship (SAR) is discussed.
Co-reporter:Dawei Chen;Dong Liu;Shi Shen;Wei Cheng
Chinese Journal of Chemistry 2012 Volume 30( Issue 7) pp:1459-1463
Publication Date(Web):
DOI:10.1002/cjoc.201200412

Abstract

Chemical examination of a Chinese gorgonian Anthogorgia sp. resulted in the isolation of seven terpenoids, including two new compounds, an rearranged serrulatane-type diterpenoid anthogorgiene P (1) and a guaiazuene-based terpenoid anthogorgiene Q (2). Anthogorgiene P (1) contains an unprecedented cubebane nucleus which is rarely found from nature. The structures of new compounds were elucidated on the basis of extensive spectroscopic methods (IR, UV, MS, CD and NMR). Compound 7 showed potent antifouling activity against the larval settlement of Balanus amphitrite, while 1 and 4 possessed moderate inhibition.

Co-reporter:Shi Shen, Huajie Zhu, Dawei Chen, Dong Liu, Leen van Ofwegen, Peter Proksch, Wenhan Lin
Tetrahedron Letters 2012 Volume 53(Issue 43) pp:5759-5762
Publication Date(Web):24 October 2012
DOI:10.1016/j.tetlet.2012.08.049
Five new cembrane-based diterpenoids, namely pavidolides A–E (1–5) were isolated from the marine soft coral Sinularia pavida, together with sarcophytin and chatancin. The structures of new compounds were determined on the basis of extensive spectroscopic data analysis. Pavidolide B (2) possesses an unprecedented 6,5,7-tricarbocyclic nucleus, whereas pavidolide C (3) is characteristic of an unusual C-5 and C-9 conjuncted cembranoid. Pavidolides C and D showed moderate antifouling activity against the larval settlement of barnacle Balanus amphitrite, while pavidolides B and C exhibited inhibitory activity against the human leukemia cell line HL-60.
Co-reporter:Shi Shen, Dong Liu, Chen Wei, Peter Proksch, Wenhan Lin
Bioorganic & Medicinal Chemistry 2012 20(24) pp: 6924-6928
Publication Date(Web):
DOI:10.1016/j.bmc.2012.10.014
Co-reporter:Jin Li, Huajie Zhu, Jinwei Ren, Zhiwei Deng, Nicole J. de Voogd, Peter Proksch, Wenhan Lin
Tetrahedron 2012 68(2) pp: 559-565
Publication Date(Web):
DOI:10.1016/j.tet.2011.11.001
Co-reporter:Daowan Lai, Shanjiang Yu, Leen van Ofwegen, Frank Totzke, Peter Proksch, Wenhan Lin
Bioorganic & Medicinal Chemistry 2011 Volume 19(Issue 22) pp:6873-6880
Publication Date(Web):15 November 2011
DOI:10.1016/j.bmc.2011.09.028
Fourteen new 9,10-secosteroids designated as astrogorgols A–N (1–14) were isolated from a Chinese gorgonian Astrogorgia sp. together with eight known analogues. The structural patterns were characterized by the presence of a sterol-based 9,10-seco nucleus containing a 3-hydroxy-10-methylphenyl ring. Astrogorgol N (14) possessing a 1,4-dien-3-one unit in ring A was biogenetically considered as an intermediate to generate diverse 9,10-secosteroids. Five compounds showed significant inhibitory activities against human tumor related protein kinases, including ALK, AXL, FAK, IGF-1R, MET wt, SRC, and VEGF-R2.
Co-reporter:Hong-Bing Liu;RuAngelie Edrada-Ebel;Rainer Ebel;Yao Wang;Barbara Schulz;Siegfried Draeger;Werner E. G. Müller;Victor Wray;Wen-Han Lin;Peter Proksch
Helvetica Chimica Acta 2011 Volume 94( Issue 4) pp:623-631
Publication Date(Web):
DOI:10.1002/hlca.201000283

Abstract

Chemical examination of the fungus Aspergillus ustus isolated from the Mediterranean sponge Suberites domuncula yielded the five new ophiobolin-type sesterterpenoids 15 and the two new pyrrolidine alkaloids 6 and 7, together with the known compound aurantiamine and cerebroside D. The structures of the new compounds were unambiguously elucidated on the basis of extensive spectroscopic-data analysis (1D- and 2D-NMR, MS, and UV) and comparison with literature data. All compounds were evaluated for their cytotoxicity against murine lymphoma cell line L5178Y.

Co-reporter:Dong Liu;Jing Xu;Wei Jiang;Zhiwei Deng;Nicole J. deVoogd;Peter Proksch
Helvetica Chimica Acta 2011 Volume 94( Issue 9) pp:1600-1607
Publication Date(Web):
DOI:10.1002/hlca.201100015

Abstract

Chemical examination of the Chinese marine sponge Xestospongia testudinaria resulted in the isolation and characterization of twelve new brominated acetylenic acids, namely xestospongienols A–L (1a1d, 2a2d, and 3a3d), together with the known analog 4. The structures of xestospongienols A–L were determined on the basis of 1D- and 2D-NMR, IR, and MS analysis in association with the modified Mosher method. The structural patterns are characteristic of brominated unbranched C16-alkyl chains containing polyene and acetylene moieties.

Co-reporter:Pengcheng Yan;Zhiwei Deng;Leen vanOfwegen;Peter Proksch
Chemistry & Biodiversity 2011 Volume 8( Issue 9) pp:1724-1734
Publication Date(Web):
DOI:10.1002/cbdv.201000244

Abstract

Chemical examination of a Chinese soft coral Lobophytum pauciflorum resulted in the isolation of seven new biscembranoids named lobophytones U–Z1 (17, resp.), together with methyl sartortuoate (8) and nyalolide (9). The structures of the new compounds were elucidated by 1D- and 2D-NMR (COSY, HSQC, HMBC, and NOESY) spectroscopic analysis in association with MS and IR data. All compounds were tested against lipopolysaccharide (LPS)-induced nitric oxide (NO) release in mouse peritoneal macrophage. Lobophytone Z (6) inhibited NO production with an IC50 value of 2.6 μM. Lobophytone H (1) showed inhibitory activities against the bacteria S. aureus and S. pneumoniae.

Co-reporter:Wei Jiang, Dong Liu, Zhiwei Deng, Nicole J. de Voogd, Peter Proksch, Wenhan Lin
Tetrahedron 2011 67(1) pp: 58-68
Publication Date(Web):
DOI:10.1016/j.tet.2010.11.045
Co-reporter:Daowan Lai, Yongxin Li, Minjuan Xu, Zhiwei Deng, Leen van Ofwegen, Peiyuan Qian, Peter Proksch, Wenhan Lin
Tetrahedron 2011 67(33) pp: 6018-6029
Publication Date(Web):
DOI:10.1016/j.tet.2011.06.029
Co-reporter:Guotao Fan, Zelin Li, Shi Shen, Yi Zeng, Yishu Yang, Minjuang Xu, Torsten Bruhn, Heike Bruhn, Joachim Morschhäuser, Gerhard Bringmann, Wenhan Lin
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 15) pp:5466-5474
Publication Date(Web):1 August 2010
DOI:10.1016/j.bmc.2010.06.052
Fifteen new DOPA-derived pyrrole alkaloids, named baculiferins A–O (2–16), were isolated from the Chinese marine sponge Iotrochota baculifera, together with the known alkaloids purpurone (1) and ningalin A (17). Most of the new compounds contain one to three O-sulfate units. Their structures were determined by extensive spectroscopic analysis including 1H and 13C NMR (COSY, HMQC, HMBC) and ESIMS data. A possible pathway for the biosynthetic origin of the isolated alkaloids is proposed, in which DOPA is assumed to be a joint biogenetic precursor. Baculiferins C, E–H, and K–N (4, 6–9, 12–15) were found to be potent inhibitors against the HIV-1 IIIB virus in both, MT4 and MAGI cells. Additional bioassay revealed that baculiferins could dramatically bind to the HIV-1 target proteins Vif, APOBEC3G, and gp41, for which structure–activity relationships are discussed.
Co-reporter:Jin Li, Bo Xu, Jinrong Cui, Zhiwei Deng, Nicole J. de Voogd, Peter Proksch, Wenhan Lin
Bioorganic & Medicinal Chemistry 2010 Volume 18(Issue 13) pp:4639-4647
Publication Date(Web):1 July 2010
DOI:10.1016/j.bmc.2010.05.029
Nine new isomalabaricane-derived natural products, globostelletins A–I (1–9), were isolated from the marine sponge Rhabdastrella globostellata, together with jaspolides F (10), rhabdastrellic acid-A (11), (−)-stellettin E (12), stellettins C (13) and D (14). The structures of these compounds were determined on the basis of extensive spectroscopic analyses and by comparison with the reported data in the literature. The inhibitory activities of compounds 1–12 against human tumor cell lines were evaluated, and their structure–activity relationships were discussed. In addition, rhabdastrellic acid-A (11) showed potent inhibition against HL-60 cells, and it induced the apoptosis of HL-60 cells in M/G2 phase. The mechanism of 11 targeting the ubiquitin-proteasome system, including the regulation of ChT-L and T-L target proteins is discussed.
Co-reporter:Cui Shi, Min-Juan Xu, Mirko Bayer, Zhi-Wei Deng, Michael H.G. Kubbutat, Wim Wätjen, Peter Proksch, Wen-Han Lin
Phytochemistry 2010 Volume 71(8–9) pp:1025
Publication Date(Web):June 2010
DOI:10.1016/j.phytochem.2010.03.007
Co-reporter:Cui Shi, Min-Juan Xu, Mirko Bayer, Zhi-Wei Deng, Michael H.G. Kubbutat, Wim Waejen, Peter Proksch, Wen-Han Lin
Phytochemistry 2010 Volume 71(Issue 4) pp:435-442
Publication Date(Web):March 2010
DOI:10.1016/j.phytochem.2009.11.008
Phenolic compounds, named integracin D (1), (7′R, 8′S, 8S)-8-hydroxyisoguaiacin (3), (2R, 3R) pinobanksin-3-caffeoylate (5) and threo-8S-7-methoxysyringylglycerol (6), respectively, were isolated from the Chinese mangrove plant Laguncularia racemosa (L) Gaertn. f. (Combretaceae), together with 23 known phenolic metabolites. Their structures were elucidated on the basis of extensive spectroscopic analyses including that of IR, UV, MS, CD, 1D and 2D NMR spectra as well as by comparison with literature data. Compound 5 showed significant anti-oxidative activity in the DPPH and TEAC free-radical-scavenging assays, while several of the phenolic compounds were tested for protein kinase inhibitory activity in an assay involving 24 different human tumor related protein kinases. Compounds 5, 7, and 23 showed potential inhibition with IC50 values between 2.2 and 3.6 μg/mL toward individual kinases. The ellagic acid derivatives were tested for insecticidal activity.Phenolic compounds, named integracin D (1), (7′R, 8′S, 8S)-8-hydroxyisoguaiacin (3), (2R, 3R) pinobanksin-3-caffeoylate (5) and threo-8S-7-methoxysyringylglycerol (6), were isolated from the Chinese mangrove plant Laguncularia racemosa (L) Gaertn. f. (Combretaceae). Their inhibitory activities against protein kinases, antioxidation, and insecticide were evaluated.
Co-reporter:Yongxin Li, Jun Liu, Shanjiang Yu, Peter Proksch, Jun Gu, Wenhan Lin
Phytochemistry 2010 Volume 71(17–18) pp:2124-2131
Publication Date(Web):December 2010
DOI:10.1016/j.phytochem.2010.08.011
Chemical examination of the stems and twigs of the mangrove plant Excoecaria agallocha L. resulted in the isolation of six ent-kaurane diterpenoids named agallochaols K–P (1–6), an atisane-type diterpenoid agallochaol Q (7), along with eight known diterpenoids (8–15). Their structures were elucidated on the basis of extensive spectroscopic analysis and by comparison of their NMR spectroscopic data with those reported in literature, in association with the biogenetic relationship with the X-ray structure of 9. Compounds 1, 5–7, 9–10, and 13 showed anti-inflammatory potency to suppress expression of NF-κB and AP-1 targeted genes including TNF-α and IL-6 induced by lipopolysaccharide (LPS) in mouse macrophages Raw 264.7 cells. In addition, compounds 1, 5–7, 9–10, and 13 block NF-κB activation, while compounds 1 and 7 block AP-1 activation dramatically, indicating these compounds possess an anti-inflammatory potential in vitro.Six ent-kaurane diterpenoids named agallochaols K–P, an atisane-type diterpenoid agallochaol Q, along with eight known diterpenoids were isolated from the mangrove plant Excoecaria agallocha L. Some of the isolated compounds suppress the expression of TNF-α and IL-6 induced by LPS, and block NF-κB and AP-1 activation.
Co-reporter:Yao Wang, RuAngelie Edrada-Ebel, Nanzad Tsevegsuren, Jandirk Sendker, Manfred Braun, Victor Wray, Wenhan Lin and Peter Proksch
Journal of Natural Products 2009 Volume 72(Issue 4) pp:671-675
Publication Date(Web):March 9, 2009
DOI:10.1021/np800782f
Chromatographic separation of a crude extract obtained from aerial parts of the Mongolian medicinal plant Scorzonera radiata yielded five new dihydrostilbenes, scorzodihydrostilbenes A−E (1−5). The structures were unambiguously elucidated on the basis of one- and two-dimensional NMR (1H, 13C, COSY, HMBC, HMQC, and ROESY) and mass spectrometric data. Compounds 1−5 exhibited antioxidative activity when analyzed in the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. For 1 and 5 the antioxidant activities were stronger than that of the well-known naturally occurring stilbene antioxidant resveratrol.
Co-reporter:Jinwei Ren, Chunmei Xue, Li Tian, Minjuan Xu, Jian Chen, Zhiwei Deng, Peter Proksch and Wenhan Lin
Journal of Natural Products 2009 Volume 72(Issue 6) pp:1036-1044
Publication Date(Web):June 10, 2009
DOI:10.1021/np900190w
Fermentation of the marine-derived fungus Trichoderma asperellum, collected from the sediment of the Antarctic Penguin Island, resulted in the isolation of six new peptaibols named asperelines A−F (1−6), which are characterized by an acetylated N-terminus and a C-terminus containing an uncommon prolinol residue. Structures were determined by extensive 1D and 2D NMR (1H−1H COSY, HMQC, HMBC, NOESY) spectroscopic data analysis combined with ESIMS/MS fragmentation. The absolute configurations of the amino acid residues possessing a chiral α-carbon and of the prolinol residue were determined to be l and S, respectively, using a new method of 1H NMR spectroscopic comparison of complexes formed between the chiral reagent Ru(d4-Por*)CO and amino acids derived from the peptaibols with those formed with reference standards.
Co-reporter:Hongbing Liu, RuAngelie Edrada-Ebel, Rainer Ebel, Yao Wang, Barbara Schulz, Siegfried Draeger, Werner E. G. Müller, Victor Wray, Wenhan Lin and Peter Proksch
Journal of Natural Products 2009 Volume 72(Issue 9) pp:1585-1588
Publication Date(Web):August 14, 2009
DOI:10.1021/np900220r
Seven new drimane sesquiterpenoids (1−3, 6−9), along with the known compounds deoxyuvidin B (4), strobilactone B (5), and RES-1149-2 (10), were obtained from cultures of the fungus Aspergillus ustus, which was isolated from the marine sponge Suberites domuncula. Their structures were established by means of spectroscopic analyses including one- and two-dimensional NMR spectroscopy and high-resolution MS. Compounds 6, 7, and 10 showed cytotoxic activity against a panel of tumor cell lines, including L5178Y, HeLa, and PC12 cells, with 7 being the most active (EC50 against L5178Y cell line: 0.6 μg/mL).
Co-reporter:Julia Kjer, Victor Wray, RuAngelie Edrada-Ebel, Rainer Ebel, Alexander Pretsch, Wenhan Lin and Peter Proksch
Journal of Natural Products 2009 Volume 72(Issue 11) pp:2053-2057
Publication Date(Web):October 16, 2009
DOI:10.1021/np900417g
Two new 10-oxo-10H-phenaleno[1,2,3-de]chromene-2-carboxylic acids, xanalteric acids I (1) and II (2), and 11 known secondary metabolites were obtained from extracts of the endophytic fungus Alternaria sp., isolated from the mangrove plant Sonneratia alba collected in China. The metabolites were confirmed to be of fungal origin, and the structures of the new natural products were unambiguously elucidated on the basis of extensive one- and two-dimensional NMR spectroscopic studies and mass spectrometric analysis. The two new compounds 1 and 2 exhibited weak antibiotic activity against multidrug-resistant Staphylococcus aureus. Altenusin (3) displayed broad antimicrobial activity against several additional multidrug-resistant bacterial and fungal strains.
Co-reporter:Jianxin Cui;Zhiwei Deng;Minjuan Xu;Peter Proksch;Qingshan Li
Helvetica Chimica Acta 2009 Volume 92( Issue 1) pp:139-150
Publication Date(Web):
DOI:10.1002/hlca.200800177
Co-reporter:Jing Xu, Julia Kjer, Jandirk Sendker, Victor Wray, Huashi Guan, RuAngelie Edrada, Werner E.G. Müller, Mirko Bayer, Wenhan Lin, Jun Wu, Peter Proksch
Bioorganic & Medicinal Chemistry 2009 17(20) pp: 7362-7367
Publication Date(Web):
DOI:10.1016/j.bmc.2009.08.031
Co-reporter:Aiying Ma, Zhiwei Deng, Leen van Ofwegen, Mirko Bayer, Peter Proksch and Wenhan Lin
Journal of Natural Products 2008 Volume 71(Issue 7) pp:1152-1160
Publication Date(Web):June 19, 2008
DOI:10.1021/np800003w
A systematic examination of the Chinese soft coral Dendronephthya sp. resulted in the isolation and characterization of 18 new cembranoid diterpenes, namely, dendronpholides A−R (2−19), along with 11-episinulariolide and an enantiomer of sandensolide. Their structures were determined through extensive spectroscopic (IR, MS, 2D NMR) data analyses and by comparison with those reported in literature. The cytotoxicity of several compounds against human tumor cell lines was also evaluated.
Co-reporter:Ting Wen, Yi Ding, Zhiwei Deng, Leen van Ofwegen, Peter Proksch and Wenhan Lin
Journal of Natural Products 2008 Volume 71(Issue 7) pp:1133-1140
Publication Date(Web):June 14, 2008
DOI:10.1021/np070640g
A bioassay-guided fractionation and chemical examination of the soft coral Sinularia flexibilis resulted in the isolation and characterization of sinulaflexiolides A−K (1−11), along with sinulariolone (12), 5-dehydrosinularolide (13), capillolide (14), sinulariolide (15), 5,8-epoxy-9-acetoxysinulariolide (16), flexibilide (17), dihydroflexibilide (18), and the enantiomer of 14-deoxycrassin (19). Their structures were determined on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with spectroscopic data reported in the literature. Sinulaflexiolides D and E showed selective inhibitory activity against the gastric gland carcinoma cell line BGC-823 at 8.5 and 0.12 μM, respectively.
Co-reporter:Fang Lv, Minjuan Xu, Zhiwei Deng, Nicole J. de Voogd, Rob W. M. van Soest, Peter Proksch and Wenhan Lin
Journal of Natural Products 2008 Volume 71(Issue 10) pp:1738-1741
Publication Date(Web):October 1, 2008
DOI:10.1021/np800324v
Chemical examination of the marine sponge Rhabdastrella aff. distincta resulted in the isolation of six new isomalabaricane triterpenes, rhabdastrellins A−F (1−6), which were present as minor components, along with stellettins L and M. Their structures were elucidated on the basis of extensive spectroscopic data analyses and comparison with spectroscopic data of known analogues. The cytotoxicity of compounds 1−6 against a small panel of human tumor cell lines was also evaluated.
Co-reporter:Ke Ma;Yi Yang;Zhiwei Deng;NicoleJ. deVoogd;Peter Proksch
Chemistry & Biodiversity 2008 Volume 5( Issue 7) pp:1313-1320
Publication Date(Web):
DOI:10.1002/cbdv.200890118

Abstract

Two new bromotyrosine alkaloids, purealidins T and U (1 and 2, resp.), along with five known bromotyrosines 37, were isolated from marine sponge Pseudoceratina sp. Their structures were elucidated on the basis of extensive spectroscopic data (CD, IR, 1D- and 2D-NMR, and MS) analysis.

Co-reporter:Yu Sun;Jie Ouyang;Zhiwei Deng;Qingshan Li
Magnetic Resonance in Chemistry 2008 Volume 46( Issue 7) pp:638-642
Publication Date(Web):
DOI:10.1002/mrc.2224

Abstract

A chemical examination of the mangrove plant Avicennia marina (Forrsk.) Vierh resulted in the isolation and characterization of five new iridoids, marinoids A–E (1–5), along with 2′-cinnamoyl-mussaenosidic acid (6), 2′-O-(4″-methoxycinnamoyl) mussaenosidic acid (7), 2′-O-(4″-hydroxycinnamoyl) mussaenosidic acid (8), and 3(R)-hydroxy-5-phenyl-4(E)-pentenoic acid (9). The structures of 1–5 were elucidated on the basis of 1D and 2D NMR (COSY, HMQC, HMBC, and NOESY) in association with IR and MS data analysis. Copyright © 2008 John Wiley & Sons, Ltd.

Co-reporter:Jianxin Cui;Jie Ouyang;Zhiwei Deng
Magnetic Resonance in Chemistry 2008 Volume 46( Issue 9) pp:894-897
Publication Date(Web):
DOI:10.1002/mrc.2273

Abstract

An unprecedented new limonoid-based alkaloid, granatoine (1), and a new phragmalin, xylocarpin L (2), along with xyloccensin Y were isolated as minor components from the fruits of the Chinese mangrove plant Xylocarpus granatum. Their structures were elucidated by extensive spectroscopic data (1D and 2D NMR) analysis. A possible biogenetic pathway for granatoine was also depicted. Copyright © 2008 John Wiley & Sons, Ltd.

Co-reporter:Aobo Guo;Li Jin;Zhiwei Deng;Shaoqing Cai;Shunxin Guo
Chemistry & Biodiversity 2008 Volume 5( Issue 4) pp:598-605
Publication Date(Web):
DOI:10.1002/cbdv.200890056

Abstract

From the roots of Stemona sessilifolia, three new stemona-type alkaloids, namely stemosessifoine (1), isooxymaistemonine (2), and isomaistemonine (3), along with eight known alkaloids (bisdehydrostemoninine, isobisdehydrostemoninine, tuberostemonine, bisdehydrotuberostemonine, bisdehydrostemoninine, isobisdehydrostemoninine, stemoninine, and protostemonine), were isolated. Their structures were determined on the basis of extensive 2D-NMR spectroscopic-data analysis and by comparison with reported values in the literature. Compound 1 is a structurally unprecedented alkaloid, and it is depicted to be bioconverted from tuberostemonine as the precursor. Isooxymaistemonine (2) showed a positive effect on the human high-density lipoprotein (HDL) receptor gene CD36 and LIMP II analogous-1 (CLA-1) at the dosage of 10 μg/ml.

Co-reporter:Liya Li, Isabel Sattler, Zhiwei Deng, Ingrid Groth, Grit Walther, Klaus-Dieter Menzel, Gudrun Peschel, Susanne Grabley, Wenhan Lin
Phytochemistry 2008 Volume 69(Issue 2) pp:511-517
Publication Date(Web):January 2008
DOI:10.1016/j.phytochem.2007.08.010
From the fermentation broth of an unidentified Phomopsis sp. (strain HKI0458) isolated from the mangrove plant Hibiscus tiliaceus, four A-seco-oleane-type triterpenes, namely 3,4-seco-olean-11,13-dien-4,15α, 22β,24-tetraol-3-oic acid (1), 3,4-seco-olean-11,13-dien-4,7β,22β,24-tetraol-3-oic acid (2), 3,4-seco- olean-13-en-4,7,15,22,24-pentaol-3-oic acid (3), and 3,4-seco-olean-13-en-4,15,22,24-tetraol-3-oic acid (4) were obtained. Their structures were elucidated by extensive spectroscopic (UV, IR, FABMS, and 2D NMR) data analyses.A-seco-oleane-type triterpenes (1–4) were isolated from the fermentation broth of a fungus Phomopsis sp. (HKI0458), which was isolated from the mangrove plant Hibiscus tiliaceus (L.). Their structures were elucidated by extensive spectroscopic data analyses.
Co-reporter:Chunmei Xue, Li Tian, Minjuan Xu, Zhiwei Deng and Wenhan Lin
The Journal of Antibiotics 2008 61(11) pp:668-674
Publication Date(Web):2008-11-01
DOI:10.1038/ja.2008.94
A new 24-membered macrolide macrolactin T (1), and a new polyene δ-lactone macrolactin U (2), along with macrolactins A, B, D, O, and S, were isolated from the cultured broth of the bacterium Bacillus marinus, which was isolated from Suaeda salsa collected in the coastline of Bohai Sea of China. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic data analyses. The inhibitory activity of macrolactins T, B and D against fungi Pyricularia oryzae and Alternaria solani, and bacteria Staphylococcus aureus is reported.
Co-reporter:Xueshi Huang;Isabel Sattler;Susanne Grabley;Liya Li;Hongzheng Fu
Magnetic Resonance in Chemistry 2006 Volume 44(Issue 6) pp:624-628
Publication Date(Web):6 APR 2006
DOI:10.1002/mrc.1802

From the stem and bark of the mangrove plant Hibiscus tiliaceus, a new friedelane-type triterpene named 27-oic-3-oxo-28-friedelanoic acid (1) together with eight known triterpenoids involving five friedelane-type derivatives was isolated. The structure of 1 was determined by extensive 2D NMR (DQF-COSY, HMQC, HMBC, and NOESY) data analyses. All the compounds were obtained from mangrove plants for the first time. Copyright © 2006 John Wiley & Sons, Ltd.

Co-reporter:Liya Li, Xiang Li, Cui Shi, Zhiwei Deng, Hongzheng Fu, Peter Proksch, Wenhan Lin
Phytochemistry 2006 Volume 67(Issue 13) pp:1347-1352
Publication Date(Web):July 2006
DOI:10.1016/j.phytochem.2006.05.016
Chemical investigation of stems of the mangrove plant, Pongamia pinnata, resulted in isolation and characterization of five structurally unusual flavonoids pongamones A–E, along with 16 known flavonoid metabolites. Their structures were determined on the basis of spectroscopic analyses and by comparison of their spectroscopic data with those of related compounds reported in the literature. Pongamones A–E were assayed against DHBV RCs DNAP and HIV-1 RT in vitro. A possible biogenetic pathway of the isolated compounds is also proposed.Chemical investigation on the stems of the mangrove plant, Pongamia pinnata, resulted in the isolation and characterization of five pongamones A–E (1–5) together with 16 known flavonoid derivatives. Their structures were determined on the basis of spectroscopic analyses and by comparison of their spectroscopic data with those reported in the literature.
Co-reporter:Shuyun Bao;Zhiwei Deng;Hongzheng Fu;Peter Proksch
Helvetica Chimica Acta 2005 Volume 88(Issue 10) pp:2757-2763
Publication Date(Web):28 OCT 2005
DOI:10.1002/hlca.200590215

Phytochemical investigation of the stems of Bruguiera sexangula var. rhynchopetala resulted in the isolation and characterization of four new and seven known secondary metabolites. The new compounds were spectroscopically identified as 17-hydroxy-16-oxobeyer-9(11)-en-19-al (1), 16,17-dihydroxy-19-nor-ent-kaur-9(11)-en-3-one (2), (16R)-13,17-epoxy-16-hydroxy-ent-kaur-9(11)-en-19-al (3), and (−)-3,4-dihydro-3-hydroxy-7-methoxy-2H-1,5-benzodithiepine-6,9-dione (10). The configurations of the known compounds brugierol (11) and isobrugierol (12) were re-investigated. Compounds 11 and 12, together with 2,6-dimethoxy-1,4-benzoquinone (13), are proposed to be degradation products of the novel, unusual disulfide 10 (Scheme).

Co-reporter:Wenhan Lin, Liya Li, Hongzheng Fu, Isabel Sattler, Xueshi Huang and Susanne Grabley
The Journal of Antibiotics 2005 58(9) pp:594-598
Publication Date(Web):
DOI:10.1038/ja.2005.81
From the mangrove plant Aegiceras comiculatum collected in South China an endophytic Streptomyces sp. was isolated. Following cultivation in a seawater-based medium, four new cyclopentenone derivatives, namely (5R) 3-amino-5-hydroxy-5-vinyl-2-cyclopenten-1-one (1), (5R) 5-hydroxy-3-[(methoxycarbonyl)amino]-5-vinyl-2-cyclopenten-1-one (2), (5R) 5-hydroxy-3-[[2-(4-hydroxyphenyl)ethyl]amino]-5-vinyl-2-cyclopenten-1-one (3), and 3-isobutylpropanamide-2-cyclopenten-1-one (4), were obtained from the fermentation broth. Their structures were elucidated by extensive spectroscopic (UV, IR, ESIMS, and 2D NMR) data analyses.
Co-reporter:Yan Zhang, Zhiwei Deng, Tianxiang Gao, Peter Proksch, Wenhan Lin
Phytochemistry 2005 Volume 66(Issue 12) pp:1465-1471
Publication Date(Web):June 2005
DOI:10.1016/j.phytochem.2005.04.018
From the stems and twigs of the mangrove plant, Ceriops tagal, seven dolabrane-type diterpenes, namely tagalsins A–G (1–7), and the norditerpene tagalsin H (8) were isolated. Their structures were established on the basis of extensive spectroscopic analysis.From the stems and twigs of the mangrove plant, Ceriops tagal, seven dolabrane-type diterpenes, namely tagalsins A–G (1–7), and the norditerpenetagalsin H (8) were isolated. Their structures were established on the basis of extensive spectroscopic analysis.
Co-reporter:Jianxin Cui, Zhiwei Deng, Jun Li, Hongzheng Fu, Peter Proksch, Wenhan Lin
Phytochemistry 2005 Volume 66(Issue 19) pp:2334-2339
Publication Date(Web):October 2005
DOI:10.1016/j.phytochem.2005.06.020
Five new phragmalin-type limonoids, xyloccensins Q–U (1–5), along with xyloccensin P were isolated from the stem bark of the mangrove plant Xylocarpus granatum. Their structures were elucidated on the basis of extensive 1D and 2D NMR as well as IR and MS spectroscopic data analyses.Five new phragmalin-type limonoids, Xyloccensins Q–U (1–5), along with xyloccensin P, were isolated from the stem and bark of the mangrove plant Xylocarpus granatum. Their structures were elucidated on the basis of extensive 1D and 2D NMR, as well as IR and MS, spectroscopic data analyses.
Co-reporter:Wei Cheng, Jinwei Ren, Qixi Huang, Hailin Long, Hongwei Jin, Liangren Zhang, Huagang Liu, Leen van Ofwegen, Wenhan Lin
Steroids (April 2016) Volume 108() pp:99-104
Publication Date(Web):1 April 2016
DOI:10.1016/j.steroids.2016.02.003
•Five new pregnane steroids isolated from Subergorgia suberosa.•Photochemical conversion to prove new structures.•Three compounds showing potent anti-flu virus activities.Five new pregnane-type steroids namely subergorgols T–X (1–5) and three known analogues (6–8) were isolated from a gorgonian coral Subergorgia suberosa. The structures of new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses, in association with photochemical transformation and ECD methods for the configurational assignment. Compounds 1–8 were evaluated for the inhibitory effects against H1N1 virus infected in MDCK cells, while subergorgols T–U and 1,2-dehydroprogesterone exerted potent inhibition against A/WSN/33 virus.Download full-size image
Co-reporter:Yan Qiu, Zhi Wei Deng, Minjuan Xu, Qingshan Li, Wen Han Lin
Steroids (22 December 2008) Volume 73(Issue 14) pp:1500-1504
Publication Date(Web):22 December 2008
DOI:10.1016/j.steroids.2008.08.006
A chemical examination of the Chinese sponge Acanthella cavernosa resulted in the isolation of three new A-ring contracted steroids, the ethyl esters of 2β-hydroxy-4,7-diketo-A-norcholest-5-en-2-oic acid (1), 24S-ethyl-2β-hydroxy-4,7-diketo-A-norcholest-5-en-2-oic acid (2), and 2β-hydroxy-4,7-diketo-24R-methyl-A-norcholest-5,22(E)-dien-2-oic acid (3), along with four other known steroids (4–7). The structures were determined on the basis of extensive spectroscopic analysis. Compounds 1–3 showed antifouling activity toward the settlement inhibition of Balanus albicostatus with the EC50 values of 8.2, 23.5, 31.6 μg/mL, respectively.
7beta-hydroxypetrosterol
3alpha-hydroxyaragusterol B
3-O-methyldiorcinol
(6Z)-6-{[2-(1,1-dimethylprop-2-en-1-yl)-1H-indol-3-yl]methylidene}-3-hydroxy-3-methylpiperazine-2,5-dione
1'-Me ether-Averantin
5alpha,6alpha-epoxy-petrosterol
2H-INDOL-2-ONE, 1,3-DIHYDRO-3-HYDROXY-3-(2-OXOPROPYL)-, (3R)-
tagalsin H
cyclo-(Pro1-Trp-Leu-Thr-Pro2-Gly-Phe)
(+)-Varitriol