Publications by authors named "Wen-Jian Lan"

37 Publications

Monascuslactams A-D, cytotoxic γ-lactams from marine fungus BB3.

Nat Prod Res 2021 May 5:1-8. Epub 2021 May 5.

School of Chemistry, Sun Yat-sen University, Guangzhou, People's Republic of China.

Amino acid-directed strategy becomes an efficient way to explore the alkaloids' biosynthetic potential of marine fungi. The metabolites of marine fungus BB3 were regulated obviously when cultured in GPY medium supplemented with L-tryptophan, L-phenylalanine, D,L-methionine, L-threonine, L-lysine, L-serine and L-valine. Four new γ-lactams, monascuslactams A-D (-), together with two known compounds pulchellalactam () and -acetylperlolyrine () were obtained. Their structures were determined by comprehensive analysis on the 1 D and 2 D NMR, HRESIMS, UV and IR data, and their absolute configurations were assigned by the experimental and calculated ECD data analysis. Compounds , and showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, GLC82, HCT116 and MDA-MB-231.
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http://dx.doi.org/10.1080/14786419.2021.1915308DOI Listing
May 2021

Monalbidins A-E, Decalins with Potential Cytotoxic Activities from Marine Derived Fungus Monascus albidus BB3.

Chem Biodivers 2021 May 16;18(5):e2100068. Epub 2021 Apr 16.

School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, P. R. China.

Five new decalins, monalbidins A-E (1, 2 and 7-9), together with 16 known compounds (3-6 and 10-21), were isolated from the AcOEt extract of marine derived fungus Monascus albidus BB3 cultured in GPY medium. Among the known compounds, 1-hydroxymonacolin L (11), dehydromonacolin J (15), 8-O-acetylmonacolin J (19) and O-acetylmonacolin K (21) were separated from natural sources for the first time. Their structures were determined by comprehensive analysis on the 1D and 2D NMR, HR-ESI-MS, UV and IR data, and their absolute configurations were assigned by experimental and calculated ECD data, and X-ray single-crystal diffraction analysis. Monalbidins C and D (7 and 8), monacolin K methyl ester (13), dehydromonacolin L (14), dehydromonacolin K (16), monacolin K (20) and O-acetylmonacolin K (21) showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, HCT116 and MDA-MB-231.
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http://dx.doi.org/10.1002/cbdv.202100068DOI Listing
May 2021

l-Tryptophan Induces a Marine-Derived sp. to Produce Indole Alkaloids with Activity against the Zika Virus.

J Nat Prod 2020 11 12;83(11):3372-3380. Epub 2020 Nov 12.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.

The effects of l-tryptophan supplementation on secondary metabolite production in the marine-derived fungus sp. L1 were investigated by culturing the fungus in GPY medium with and without the amino acid. HPLC analysis of the products showed distinct metabolite profiles between the two cultures. The H NMR spectrum of the EtOAc extract of the culture supplemented with l-tryptophan displayed a series of characteristic aromatic proton signals (δ 6.50-8.50) and NH signals (δ 10.50-11.50) that were not observed in those from cultures not supplemented with l-tryptophan. Subsequently, 23 distinct indole alkaloids, including six new compounds, fusaindoterpenes A and B ( and ), fusariumindoles A-C (-), and (±)-isoalternatine A (), together with 17 known compounds, were obtained from this culture. Fusaindoterpene A () contains a 6/9/6/6/5 heterocyclic system. Their chemical structures were determined by analysis of HRMS, NMR spectroscopy, optical rotation calculation, ECD calculation, and single-crystal X-ray diffraction data. Compounds , , and displayed inhibitory activity against the Zika virus (ZIKV) in a standard plaque assay with EC values of 7.5, 4.2, and 5.0 μM, respectively, while not showing significant cell cytotoxicity against the A549 adenocarcinomic human alveolar basal epithelial cell line.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00717DOI Listing
November 2020

Potential Antidiabetic Fumiquinazoline Alkaloids from the Marine-Derived Fungus F41-1.

J Nat Prod 2020 04 4;83(4):1082-1091. Epub 2020 Mar 4.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China.

Fumiquinazoline alkaloids have attracted much attention from medicinal and natural product chemists due to their interesting structures and biological potential. In this study, three new and 12 known fumiquinazoline alkaloids were isolated and characterized from the marine fungus F41-1. The structures of the new compounds and their absolute configurations were determined using NMR spectroscopy, ECD, and OR calculations. The compounds were evaluated for their antidiabetic potential by determining their triglyceride-promoting activity using 3T3-L1 adipocytes. One of the new compounds, scequinadoline J (), as well as scequinadolines D () and E (), was found to promote triglyceride accumulation in 3T3-L1 cells. Scequinadoline D () demonstrated the most potent activity, with an EC value of 0.27 ± 0.03 μM. Quantitative polymerase chain reaction experiments suggested that scequinadoline D () acts through activation of the PPARγ pathway. It stimulated the mRNA expression of PPARγ, AMPKα, C/EBPα, LXRα, SCD-1, and FABP4. In addition, its triglyceride-promoting efficacy could be blocked by a double dose of the PPARγ antagonist GW9662. These results indicated that scequinadoline D () is a potent insulin sensitizer that targets adipocytes and may be useful for the treatment of type 2 diabetes mellitus after further investigation.
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http://dx.doi.org/10.1021/acs.jnatprod.9b01096DOI Listing
April 2020

Monarubins A-C from the Marine Shellfish-Associated Fungus BB5.

Mar Drugs 2020 Feb 3;18(2). Epub 2020 Feb 3.

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Three new compounds, monarubins A-C (, and ), together with ten known compounds, including four alkaloids (-), two isocoumarins ( and ) and four polyketides (-), were isolated from marine shellfish-associated fungus BB5. The structures were determined on the basis of the 1D and 2D NMR, MS, UV and IR data. The absolute configurations of compounds , and were determined by ECD calculations. The NMR data of compounds deoxyhydroxyaspergillic acid () and 2-hydroxy-6-(1-hydroxy-1-methylpropyl)-3--buthylpyrazine () were first reported. All of the isolated compounds were evaluated for their cytotoxic activities against human nasopharyngeal carcinoma cell lines CNE1, CNE2, SUNE1 and HONE1 and hepatocellular carcinoma cell lines QGY7701 and HepG2. Monarubin B () displayed potent cytotoxicities against the cancer cell lines HepG2 and QGY7701 with IC values of 1.72 and 0.71 μΜ, respectively; lunatinin () showed moderate cytotoxic activities against the cancer cell lines HepG2, QGY7701 and SUNE1 with the IC values of 9.60, 7.12 and 28.12 μΜ, respectively.
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http://dx.doi.org/10.3390/md18020100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073648PMC
February 2020

l-Phenylalanine Alters the Privileged Secondary Metabolite Production in the Marine-Derived Fungus F1-1.

J Nat Prod 2020 01 30;83(1):79-87. Epub 2019 Dec 30.

School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou 510006 , People's Republic of China.

The effects of a single-amino-acid culture strategy on secondary metabolite production in the marine-derived fungus F1-1 were investigated by culturing the fungus in GPY medium supplemented or not supplemented with l-phenylalanine. A suite of secondary metabolites, including seven terpenoids (-) and one polyketide (), among which are four new compounds, harziandione A (), cyclonerodiols A and B (, ), and trichodermaerin A (), were isolated from the GPY medium without l-phenylanine, whereas 18 aromatic compounds (-), including six new compounds, trichoderolides A-F (, , and -), were isolated from the culture grown in the GPY medium with l-phenylalanine. The structures of the new compounds were determined by high-resolution mass spectrometry, NMR spectroscopic analysis, optical rotation calculations, chemical methods, and X-ray crystallography. Compounds , , , and exhibited cytotoxic activities against MDA-MB-435 human melanocyte cancer cells. Compound was cytotoxic to A549 adenocarcinomic human alveolar basal epithelial cells.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00710DOI Listing
January 2020

A pair of novel bisindole alkaloid enantiomers from marine fungus sp. XBB-9.

Nat Prod Res 2021 May 22;35(9):1497-1503. Epub 2019 Aug 22.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.

A preliminary research on the marine fungus sp. XBB-9 resulted in a pair of novel bisindole alkaloid enantiomers, (+)- and (-)-fusaspoid A (/) and 12 diverse compounds. One strain many compound (OSMAC) method was used to enhance as many biosynthetic pathways as possible. The structures of the compounds were elucidated by spectroscopic analysis, and the absolute configuration of was determined by X-ray single-crystal diffraction analysis. Compounds and were tested for cytotoxic activity against HCT-15, RKO cell lines, but were inactive. Compounds and were the first example of bisindole alkaloids isolated from fungus sp. XBB-9.
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http://dx.doi.org/10.1080/14786419.2019.1655416DOI Listing
May 2021

Reactive oxygen species altering the metabolite profile of the marine-derived fungus F31-1.

Nat Prod Res 2021 Jan 19;35(1):41-48. Epub 2019 Jun 19.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

To investigate the influence of reactive oxygen species (ROS) on the secondary metabolites of the marine-derived fungus F31-1, hydrogen peroxide (HO) was added to the GPY culture medium. The HPLC chromatogram of the EtOAc extract of the culture broth was distinct from that of the HO free GPY medium. Further study of the metabolites in the GPY medium with HO resulted in the discovery of eight known compounds. Among them, (22)-5α, 8α-epidioxyergosta-6, 22-dien-3-ol () and ergosta-4,6,8(14),22-tetraene-3-one () were present in the highest concentration, while ergosterol and diketopiperazines are abundant in the HO free medium. Additionally, a new compound, dichocetide D () containing a chlorine element and a known ergosterol () were isolated from the HO free medium. (22)-5α, 8α-epidioxyergosta-6, 22-dien-3-ol () exhibited moderate cytotoxic activity against human prostate cancer cell line LNCaP-C4-2B.
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http://dx.doi.org/10.1080/14786419.2019.1611816DOI Listing
January 2021

Exploration of Indole Alkaloids from Marine Fungus F44-1 Using an Amino Acid-Directed Strategy.

Mar Drugs 2019 Jan 23;17(2). Epub 2019 Jan 23.

School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China.

The composition of the culture medium has great influence on the metabolite production of the marine fungus F44-1. By adding amino acids to GPY culture medium, two new bisindole alkaloids, pseudboindoles A and B ( and ), together with 11 known indole alkaloids were isolated from the culture broth. Their structures were elucidated by comprehensive analysis of the NMR, MS, IR, and UV spectra. The 3,3'-cyclohexylidenebis(1-indole) () showed cytotoxic activity against various cancer cell lines.
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http://dx.doi.org/10.3390/md17020077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410255PMC
January 2019

Linear Triquinane Sesquiterpenoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis.

Molecules 2018 Aug 21;23(9). Epub 2018 Aug 21.

School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China.

Linear triquinane sesquiterpenoids represent an important class of natural products. Most of these compounds were isolated from fungi, sponges, and soft corals, and many of them displayed a wide range of biological activities. On account of their structural diversity and complexity, linear triquinane sesquiterpenoids present new challenges for chemical structure identification and total synthesis. 118 linear triquinane sesquiterpenoids were classified into 8 types, named types I⁻VIII, based on the carbon skeleton and the position of carbon substituents. Their isolation, structure elucidations, biological activities, and chemical synthesis were reviewed. This paper cited 102 articles from 1947 to 2018.
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http://dx.doi.org/10.3390/molecules23092095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225328PMC
August 2018

Polyketides and Alkaloids from the Marine-Derived Fungus F31-1 and the Antiviral Activity of Scequinadoline A against Dengue Virus.

Mar Drugs 2018 Jul 6;16(7). Epub 2018 Jul 6.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

In our continuous chemical investigation on the marine-derived fungus F31-1, two new polyketides dichocetides B-C (, ), two new alkaloids dichotomocejs E-F (, ), and three known fumiquinozalines: scequinadoline A (), quinadoline A (), and scequinadoline E () were discovered from the culture broth and the mycelium in the culture medium, by the addition of l-tryptophan and l-phenylalanine. Their chemical structures were established by one dimensional (1D), two dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) data. Among them, scequinadoline A () exhibited significant inhibitory activity against dengue virus serotype 2 production by standard plaque assay, equivalent to the positive control andrographlide. Scequinadoline A () possesses the potential for further development as a dengue virus inhibitor.
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http://dx.doi.org/10.3390/md16070229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071211PMC
July 2018

Diverse Secondary Metabolites from the Marine-Derived Fungus Dichotomomyces cejpii F31-1.

Mar Drugs 2017 Nov 1;15(11). Epub 2017 Nov 1.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

By adding l-tryptophan and l-phenylalanine to GPY medium, twenty-eight compounds, including amides, polyketides, a sesquiterpenoid, a diterpenoid, a meroterpenoid, diketopiperazines, β-carbolines, fumiquinazolines, and indole alkaloids, were discovered from the marine-derived fungus F31-1, demonstrating the tremendous biosynthetic potential of this fungal strain. Among these compounds, four amides dichotomocejs A-D (-), one polyketide dichocetide A (), and two diketopiperazines dichocerazines A-B ( and ) are new. The structures of these new compounds were determined by interpreting detailed spectroscopic data as well as calculating optical rotation values and ECD spectra. Obviously, can effectively use an amino acid-directed strategy to enhance the production of nitrogen-containing compounds. Dichotomocej A () displayed moderate cytotoxicity against the human rhabdomyosarcoma cell line RD with an IC value of 39.1 µM, and pityriacitrin () showed moderate cytotoxicity against the human colon carcinoma cell line HCT116 with an IC value of 35.1 µM.
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http://dx.doi.org/10.3390/md15110339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706029PMC
November 2017

Two new hirsutane-type sesquiterpenoids chondrosterins N and O from the marine fungus Chondrostereum sp.

Nat Prod Res 2018 Jul 19;32(13):1578-1582. Epub 2017 Oct 19.

a School of Chemistry , Sun Yat-sen University , Guangzhou , China.

The marine fungus Chondrostereum sp. was collected from a soft coral Sarcophyton tortuosum from the South China Sea. This fungus was cultured in glucose-peptone-yeast (GPY) medium and the culture broth was extracted with EtOAc. By the method of H NMR pre-screening and tracing the diagnostic proton signals of the methyl groups, two new hirsutane-type sesquiterpenoids, chondrosterins N and O (1 and 2) were isolated from the metabolite extracts. Their structures were elucidated on the basis of MS, 1D and 2D NMR data.
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http://dx.doi.org/10.1080/14786419.2017.1389935DOI Listing
July 2018

Amino Acid-Directed Strategy for Inducing the Marine-Derived Fungus Scedosporium apiospermum F41-1 to Maximize Alkaloid Diversity.

Org Lett 2017 09 24;19(18):4888-4891. Epub 2017 Aug 24.

School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, China.

By feeding various amino acids to the marine fungus Scedosporium apiospermum F41-1, 22 diverse alkaloids, including 14 new compounds, were obtained. Scedapins A-E (1-5) possess a rare skeleton of a pyrazinoquinazolinedione and an imidazoindolone/indolone linked by a tetrahydrofuran ring. Scedapin C (3) is the first example of fumiquinazoline that contains an aminosulfonyl group. Their structures were determined by HRMS, NMR, ECD calculations and X-ray single-crystal diffraction analysis. The biosynthetic pathways of fumiquinazolines 1-18 were proposed. Scedapin C (3) and scequinadoline D (8) displayed significant antiviral activity against hepatitis C.
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http://dx.doi.org/10.1021/acs.orglett.7b02238DOI Listing
September 2017

Secondary Metabolites from the Marine-Derived Fungus Dichotomomyces sp. L-8 and Their Cytotoxic Activity.

Molecules 2017 Mar 11;22(3). Epub 2017 Mar 11.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Bioassay-guided isolation of the secondary metabolites from the fungus . L-8 associated with the soft coral led to the discovery of two new compounds, dichotones A and B ( and ), together with four known compounds including dichotocejpin C (), bis--norgliovictin (), bassiatin () and (3,6)-bassiatin (). The structures of these compounds were determined by 1D, 2D NMR and mass spectrometry. (3,6)bassiatin () displayed significant cytotoxic activities against the human breast cancer cell line MDA-MB-435 and the human lung cancer cell line Calu3 with IC values of 7.34 ± 0.20 and 14.54 ± 0.01 μM, respectively, while bassiatin (), the diastereomer of compound , was not cytotoxic.
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http://dx.doi.org/10.3390/molecules22030444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155177PMC
March 2017

Two New Pyripyropenes from the Marine Fungus Fusarium lateritium 2016F18-1.

Chem Biodivers 2017 Mar 27;14(3). Epub 2017 Feb 27.

School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, P. R. China.

Two new pyripyropenes, 13-dehydroxy-1,11-deacetylpyripyropene A (1) and 1-deacetylpyripyropene A (2), together with six known compounds, were isolated from a marine fungus Fusarium lateritium 2016F18-1 which was associated with the sponge Phyllospongia foliascens. Their structures were established mainly based on NMR and MS data. Their cytotoxic activities against human cancer cells CNE1, CNE2, HONE1, SUNE1, GLC82, and HL7702 were evaluated.
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http://dx.doi.org/10.1002/cbdv.201600298DOI Listing
March 2017

Additional New Cytotoxic Triquinane-Type Sesquiterpenoids Chondrosterins K-M from the Marine Fungus Chondrostereum sp.

Mar Drugs 2016 Aug 26;14(9). Epub 2016 Aug 26.

School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.

By the method of ¹H NMR prescreening and tracing the diagnostic proton signals of the methyl groups, three additional new triquinane-type sesquiterpenoids-chondrosterins K-M (1-3) and the known sesquiterpenoid anhydroarthrosporone (4)-were isolated from the marine fungus Chondrostereum sp. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Chondrosterin K is a rare hirsutane sesquiterpenoid, in which a methyl group was migrated from C-2 to C-6 and has a double bond between C-2 and C-3. Compounds 1-3 showed significant cytotoxicities against various cancer cell lines in vitro.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039528PMC
http://dx.doi.org/10.3390/md14090157DOI Listing
August 2016

Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK.

Neurochem Res 2016 Sep 9;41(9):2267-77. Epub 2016 May 9.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.

Oxidative stress mediates the pathogenesis of neurodegenerative disorders. Gartanin, a natural xanthone of mangosteen, possesses multipharmacological activities. Herein, the neuroprotection capacity of gartanin against glutamate-induced damage in HT22 cells and its possible mechanism(s) were investigated for the first time. Glutamate resulted in cell death in a dose-dependent manner and supplementation of 1-10 µM gartanin prevented the detrimental effects of glutamate on cell survival. Additional investigations on the underlying mechanisms suggested that gartanin could effectively reduce glutamate-induced intracellular ROS generation and mitochondrial depolarization. We further found that gartanin induced HO-1 expression independent of nuclear factor erythroid-derived 2-like 2 (Nrf2). Subsequent studies revealed that the inhibitory effects of gartanin on glutamate-induced apoptosis were partially blocked by small interfering RNA-mediated knockdown of HO-1. Finally, the protein expression of phosphorylation of AMP-activated protein kinase (AMPK) and its downstream signal molecules, Sirtuin activator (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), increased after gartanin treatment. Taken together, these findings suggest gartanin is a potential neuroprotective agent against glutamate-induced oxidative injury partially through increasing Nrf-2-independed HO-1 and AMPK/SIRT1/PGC-1α signaling pathways.
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http://dx.doi.org/10.1007/s11064-016-1941-xDOI Listing
September 2016

Two Additional New Compounds from the Marine-Derived Fungus Pseudallescheria ellipsoidea F42-3.

Molecules 2016 Apr 1;21(4):442. Epub 2016 Apr 1.

School of Pharmacy, Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Two additional new compounds, pseudellone D (1) and (5S,6S)-dihydroxylasiodiplodin (3), along with the two known compounds lasiodipline F (2), (5S)-hydroxylasiodiplodin (4) were isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3 associated with the soft coral Lobophytum crassum. Their structures, including absolute configurations, were elucidated on the basis of the corresponding spectroscopic data and electronic circular dichroism (ECD) spectra.
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http://dx.doi.org/10.3390/molecules21040442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274254PMC
April 2016

Natural Xanthones from Garcinia mangostana with Multifunctional Activities for the Therapy of Alzheimer's Disease.

Neurochem Res 2016 Jul 2;41(7):1806-17. Epub 2016 Apr 2.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.

Natural xanthones have diversity pharmacological activities. Here, a series of xanthones isolated from the pericarps of Garcinia mangostana Linn, named α-Mangostin, 8-Deoxygartanin, Gartanin, Garciniafuran, Garcinone C, Garcinone D, and γ-Mangostin were investigated. Biological screening performed in vitro and in Escherichia coli cells indicated that most of the xanthones exhibited significant inhibition of self-induced β-amyloid (Aβ) aggregation and also β-site amyloid precursor protein-cleaving enzyme 1, acted as potential antioxidants and biometal chelators. Among these compounds, α-Mangostin, Gartanin, Garcinone C and γ-Mangostin showed better antioxidant properties to scavenge Diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) free radical than Trolox, and potent neuroprotective effects against glutamate-induced HT22 cell death partly by up-regulating HO-1 protein level and then scavenging reactive oxygen species. Moreover, Gartanin, Garcinone C and γ-Mangostin could be able to penetrate the blood-brain barrier (BBB) in vitro. These findings suggest that the natural xanthones have multifunctional activities against Alzheimer's disease (AD) and could be promising compounds for the therapy of AD.
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http://dx.doi.org/10.1007/s11064-016-1896-yDOI Listing
July 2016

Five New Cytotoxic Metabolites from the Marine Fungus Neosartorya pseudofischeri.

Mar Drugs 2016 Jan 13;14(1):18. Epub 2016 Jan 13.

School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.

The marine fungus Neosartorya pseudofischeri was isolated from Acanthaster planci from the South China Sea. In a preliminary bioactivity screening, the crude methanol extract of the fungal mycelia showed significant inhibitory activity against the Sf9 cell line from the fall armyworm Spodoptera frugiperda. Five novel compounds, including 5-olefin phenylpyropene A (1), 13-dehydroxylpyripyropene A (4), deacetylsesquiterpene (7), 5-formyl-6-hydroxy-8-isopropyl-2- naphthoic acid (9) and 6,8-dihydroxy-3-((1E,3E)-penta-1,3-dien-1-yl)isochroman-1-one (10), together with eleven known compounds, phenylpyropene A (2) and C (3), pyripyropene A (5), 7-deacetylpyripyropene A (6), (1S,2R,4aR,5R,8R,8aR)-1,8a-dihydroxy-2-acetoxy-3,8-dimethyl-5- (prop-1-en-2-yl)-1,2,4a, 5,6,7,8,8a-octahydronaphthalene (8), isochaetominine C (11), trichodermamide A (12), indolyl-3-acetic acid methyl ester (13), 1-acetyl-β-carboline (14), 1,2,3,4-tetrahydro-6-hydroxyl-2-methyl-l,3,4-trioxopyrazino[l,2-a]-indole (15) and fumiquinazoline F (16), were obtained. The structures of these compounds were determined mainly by MS and NMR data. The absolute configuration of 9 was assigned by the single-crystal X-ray diffraction studies. Compounds 1-11 and 15 showed significant cytotoxicity against the Sf9 cells from S. frugiperda.
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http://dx.doi.org/10.3390/md14010018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728515PMC
January 2016

Pseudellones A-C, Three Alkaloids from the Marine-Derived Fungus Pseudallescheria ellipsoidea F42-3.

Org Lett 2015 Nov 9;17(21):5156-9. Epub 2015 Oct 9.

School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou 510006, China.

Pseudellones A and B (1 and 2), a pair of irregularly bridged epimonothiodiketopiperazine diastereomers constructed from unusual 3-indolylglycine and alanine residues, and an alkaloid pseudellone C (3) possessing a unique skeleton were isolated from the marine-derived fungus Pseudallescheria ellipsoidea F42-3. Their structures were determined by spectroscopic data, ECD calculation, and X-ray single crystal diffraction. The biogenetic pathways of 1-3 were proposed, and 1H-indole-3-carboxylic acid (4), a plausible biosynthetic intermediate, was coisolated.
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http://dx.doi.org/10.1021/acs.orglett.5b02311DOI Listing
November 2015

Two chlorinated benzofuran derivatives from the marine fungus Pseudallescheria boydii.

Nat Prod Commun 2015 Apr;10(4):621-2

The marine fungus Pseudallescheria boydii was isolated from the inner tissue of the starfish Acanthaster planci. This fungus was cultured in a high salinity glucose-peptone-yeast extract (GPY) medium. Two new chlorinated benzofuran derivatives, 6-chloro-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5 hydroxybenzofuran (1) and 7-chloro-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (2), were obtained from the extract of the culture broth. Their structures were determined by analysis of the NMR and MS data.
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April 2015

Exploring the chemodiversity and biological activities of the secondary metabolites from the marine fungus Neosartorya pseudofischeri.

Mar Drugs 2014 Nov 24;12(11):5657-76. Epub 2014 Nov 24.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

The production of fungal metabolites can be remarkably influenced by various cultivation parameters. To explore the biosynthetic potentials of the marine fungus, Neosartorya pseudofischeri, which was isolated from the inner tissue of starfish Acanthaster planci, glycerol-peptone-yeast extract (GlyPY) and glucose-peptone-yeast extract (GluPY) media were used to culture this fungus. When cultured in GlyPY medium, this fungus produced two novel diketopiperazines, neosartins A and B (1 and 2), together with six biogenetically-related known diketopiperazines,1,2,3,4-tetrahydro-2, 3-dimethyl-1,4-dioxopyrazino[1,2-a]indole (3), 1,2,3,4-tetrahydro-2-methyl-3-methylen e-1,4-dioxopyrazino[1,2-a]indole (4), 1,2,3,4-tetrahydro-2-methyl-1,3,4-trioxopyrazino[1,2-a] indole (5), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio)gliotoxin (11), didehydrobisdethiobis(methylthio)gliotoxin (12) and N-methyl-1H-indole-2-carboxamide (6). However, a novel tetracyclic-fused alkaloid, neosartin C (14), a meroterpenoid, pyripyropene A (15), gliotoxin (7) and five known gliotoxin analogues, acetylgliotoxin (8), reduced gliotoxin (9), 6-acetylbis(methylthio)gliotoxin (10), bisdethiobis(methylthio) gliotoxin (11) and bis-N-norgliovictin (13), were obtained when grown in glucose-containing medium (GluPY medium). This is the first report of compounds 3, 4, 6, 9, 10 and 12 as naturally occurring. Their structures were determined mainly by MS, 1D and 2D NMR data. The possible biosynthetic pathways of gliotoxin-related analogues and neosartin C were proposed. The antibacterial activity of compounds 2-14 and the cytotoxic activity of compounds 4, 5 and 7-13 were evaluated. Their structure-activity relationships are also preliminarily discussed.
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http://dx.doi.org/10.3390/md12115657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245550PMC
November 2014

Pseudaboydins A and B: novel isobenzofuranone derivatives from marine fungus Pseudallescheria boydii associated with starfish Acanthaster planci.

Mar Drugs 2014 Jul 14;12(7):4188-99. Epub 2014 Jul 14.

Institute of Chinese Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Two novel isobenzofuranone derivatives, pseudaboydins A (1) and B (2), along with five known compounds, including (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-hydroxybenzofuran (3), (R)-2-(2-hydroxypropan-2-yl)-2,3-dihydro-5-methoxybenzofuran (4), 3,3'-dihydroxy-5,5'-dimethyldiphenyl ether (5), 3-(3-methoxy-5-methylphenoxy)-5-methylphenol (6) and (-)-regiolone (7), were isolated from the culture broth of the marine fungus, Pseudallescheria boydii, associated with the starfish, Acanthaster planci. Their structures were elucidated primarily based on NMR and MS data. The absolute configurations of 1-4 were determined by CD spectroscopy and single-crystal X-ray diffraction studies. The cytotoxic and antibacterial activities of 1-4 were evaluated. Pseudaboydin A (1) showed moderate cytotoxic activity against human nasopharyngeal carcinoma cell line HONE1, human nasopharyngeal carcinoma cell line SUNE1 and human glandular lung cancer cell line GLC82 with IC50 values of 37.1, 46.5 and 87.2 μM, respectively.
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http://dx.doi.org/10.3390/md12074188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113822PMC
July 2014

Cytotoxic prenylated xanthones from the pericarps of Garcinia mangostana.

Molecules 2014 Feb 6;19(2):1820-7. Epub 2014 Feb 6.

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

Bioassay-guided fractionation of an ethanol extract of the pericarps of Garcinia mangostana led to the isolation of two new prenylated xanthones, named 1,3,7-trihydroxy-2-(3-methyl-2-butenyl)-8-(3-hydroxy-3-methylbutyl)-xanthone (1) and 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), together with the five known compounds garcinones C (3) and D (4), gartanin (5), xanthone I (6), and γ-mangostin (7). Their structures were elucidated primarily based on MS and NMR data. Compounds 1-7 showed significant cytotoxic activities against various human cancer cell lines.
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http://dx.doi.org/10.3390/molecules19021820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271135PMC
February 2014

Induced marine fungus Chondrostereum sp. as a means of producing new sesquiterpenoids chondrosterins I and J by using glycerol as the carbon source.

Mar Drugs 2014 Jan 7;12(1):167-75. Epub 2014 Jan 7.

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

Chondrostereum sp., a marine fungus isolated from a soft coral Sarcophyton tortuosum, can yield hirsutane framework sesquiterpenoids. However, the metabolites profiles vary dramatically with the composition change of the culture media. This fungus was cultured in a liquid medium containing glycerol as the carbon source, and two new metabolites, chondrosterins I and J (1 and 2), were obtained. Their structures were elucidated primarily based on MS, NMR and X-ray single-crystal diffraction data. By comparison with the known hirsutane sesquiterpenoids, chondrosterins I and J have unique structural features, including a methyl was migrated from C-2 to C-6, and the methyl at C-3 was carboxylated. Compound 2 exhibited potent cytotoxic activities against the cancer cell lines CNE-1 and CNE-2 with the IC50 values of 1.32 and 0.56 μM.
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http://dx.doi.org/10.3390/md12010167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917267PMC
January 2014

Trichodermaerin, a new diterpenoid lactone from the marine fungus Trichoderma erinaceum associated with the sea star Acanthaster planci.

Nat Prod Commun 2013 Jan;8(1):67-8

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China.

Trichodermaerin (1), a novel diterpenoid lactone, together with the known compound, harziandione (2) were isolated from the culture broth of the fungus Trichoderma erinaceum associated with the sea star Acanthaster planci. Their structures were determined by analysis of the NMR and MS data. 1 was the Baeyer-Villiger monooxygenase catalyzed oxidation product of 2. Compound 2 did not show cytotoxic activities against various cancer cell lines.
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January 2013

Isolation and structural elucidation of chondrosterins F-H from the marine fungus Chondrostereum sp.

Mar Drugs 2013 Feb 22;11(2):551-8. Epub 2013 Feb 22.

School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

The marine fungus Chondrostereum sp. was collected from a soft coral of the species Sarcophyton tortuosum from the South China Sea. Three new compounds, chondrosterins F-H (1, 4 and 5), together with three known compounds, incarnal (2), arthrosporone (3), and (2E)-decene-4,6,8-triyn-1-ol (6), were isolated. Their structures were elucidated primarily based on NMR and MS data. Incarnal (2) exhibited potent cytotoxic activity against various cancer cell lines.
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http://dx.doi.org/10.3390/md11020551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640397PMC
February 2013

Hirsutanol A, a novel sesquiterpene compound from fungus Chondrostereum sp., induces apoptosis and inhibits tumor growth through mitochondrial-independent ROS production: hirsutanol A inhibits tumor growth through ROS production.

J Transl Med 2013 Feb 8;11:32. Epub 2013 Feb 8.

State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road East, Guangzhou 510060, China.

Background: Hirsutanol A is a novel sesquiterpene compound purified from fungus Chondrostereum sp. in Sarcophyton tortuosum. Our previous studies had demonstrated that hirsutanol A exhibited potent cytotoxic effect on many kinds of cancer cell lines. In the current study, the antitumor activity of hirsutanol A and its molecular mechanisms were investigated.

Methods: Hirsutanol A induced growth inhibition and apoptotic cell death of human colon cancer SW620 cells and human breast cancer MDA-MB-231cells were determined using MTT assay and flow cytometry assay, respectively. The effect of hirsutanol A on intrinsic ROS level and change in mitochondrial membrane potential (△ψm) of different cell lines were also measured by flow cytometry assay. The function of JNK was compromised by JNK siRNA or JNK inhibitor SP600125. The expression of cytochrome c, p-JNK, p-c-Jun after treatment with hirsutanol A were detected by Western blot analysis. Finally, the in vivo anti-tumor effect of hirsutanol A was examined in human cancer cell SW620 xenograft model.

Results: The results showed that hirsutanol A significantly induced apoptosis, mitochondrial-independent increase of Reactive Oxygen Species (ROS) level, change of mitochondrial membrane potential, release of cytochrome c in human cancer cells. Preventing increase of ROS level using the potent antioxidant N-acetyl-L-cysteine (NAC) markedly decreased hirsutanol A-induced apoptosis. In addition, JNK signaling pathway was activated by hirsutanol A through elevating ROS level. Blockade of JNK signaling pathway by JNK specific inhibitor SP600125 enhanced apoptosis and hirsutanol A-induced ROS accumulation. Also, hirsutanol A exhibited antitumor activity in human cancer cell SW620 xenograft model.

Conclusion: These data suggested that hirsutanol A inhibited tumor growth through triggering ROS production and apoptosis.
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http://dx.doi.org/10.1186/1479-5876-11-32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637523PMC
February 2013