Publications by authors named "Sang-Jip Nam"

120 Publications

Saccharobisindole, Neoasterric Methyl Ester, and 7-Chloro-4(1H)-quinolone: Three New Compounds Isolated from the Marine Bacterium sp.

Mar Drugs 2021 Dec 29;20(1). Epub 2021 Dec 29.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, CA 92093-0204, USA.

Analysis of the chemical components from the culture broth of the marine bacterium sp. CNQ-490 has yielded three novel compounds: saccharobisindole (), neoasterric methyl ester (), and 7-chloro-4()-quinolone (), in addition to acremonidine E (), pinselin (), penicitrinon A (), and penicitrinon E (). The chemical structures of the three novel compounds were elucidated by the interpretation of 1D, 2D nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS) data. Compound generated weak inhibition activity against KCTC2441 and KCTC1927 at concentrations of 32 μg/mL and 64 μg/mL, respectively, whereas compounds and did not have any observable effects. In addition, compound displayed weak anti-quorum sensing (QS) effects against KCTC1927 and SCO560.
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http://dx.doi.org/10.3390/md20010035DOI Listing
December 2021

Erythrobacter rubeus sp. nov., a carotenoid-producing alphaproteobacterium isolated from coastal seawater.

Arch Microbiol 2022 Jan 8;204(2):125. Epub 2022 Jan 8.

Department of Chemistry and Nanoscience, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul, 03760, Republic of Korea.

A study based on a polyphasic taxonomic approach was carried out to identify and classify a novel marine alphaproteobacterium, designated as KMU-140, isolated from coastal seawater collected at Jeju Island, Republic of Korea. Cells of strain KMU-140 were spherical, Gram-stain-negative, reddish-orange colored, strictly aerobic, catalase- and oxidase-positive, non-motile, and chemoorganoheterotrophic. The novel isolate was able to grow at NaCl concentrations of 0-5%, pH 6.0-9.5, and 10-45 °C. A phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KMU-140 belongs to the family Erythrobacteraceae and was most closely related to Erythrobacter longus OCh101 (98.7%). Strain KMU-140 contained ubiquinone-10 (Q-10) as the only respiratory quinone and C18:1 ω7c, iso-C18:0, and C16:0 as the main (> 10%) cellular fatty acids. Strain KMU-140 produced carotenoid compounds that rendered the cell biomass a reddish-orange color. The assembled draft genome size of strain KMU-140 was 3.04 Mbp with G + C content of 60.6 mol%. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and average amino acid identity (AAI) values of KMU-140 and the species of the genus Erythrobacter were found to be 76.6-78.4%, 14.0-18.7%, and 69.6-77.8%, respectively. Phosphatidylethanolamine, phosphatidylglycerol, an unidentified phospholipid, and two unidentified lipids were identified as major polar lipids. On the basis of the polyphasic taxonomic features presented, the strain is considered to represent a novel species of the genus Erythrobacter for which the name Erythrobacter rubeus sp. nov. is proposed. The type strain of E. rubeus sp. nov. is KMU-140 (= KCCM 90479 = NBRC 115159).
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http://dx.doi.org/10.1007/s00203-021-02736-2DOI Listing
January 2022

Gwanakosides A and B, 6-Deoxy-α-l-talopyranose-Bearing Aromatic Metabolites from a sp. and Coculture with sp.

J Nat Prod 2021 Dec 21. Epub 2021 Dec 21.

Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Single-strain cultivation of a mountain soil-derived sp. GA02 and its coculture with sp. GA02N produced two aromatic products, gwanakosides A and B ( and , respectively). Their spectroscopic analysis revealed that is a new dichlorinated naphthalene glycoside and is a pentacyclic aromatic glycoside. The assignment of the two chlorine atoms in was confirmed by the analysis of its band-selective CLIP-HSQMBC spectrum. The sugars in the gwanakosides were identified as 6-deoxy-α-l-talopyranose based on H-H coupling constants, Rotating frame Overhauser enhancement spectroscopy (ROESY) NMR correlations, and chemical derivatization followed by spectroscopic and chromatographic analyses. The absolute configuration of , whose production was enhanced approximately 100-fold in coculture, was proposed based on a quantum mechanics-based chemical shift analysis method, DP4 calculations, and the chemically determined configuration of 6-deoxy-α-l-talopyranose. Gwanakoside A displayed inhibitory activity against pathogenic bacteria, including (MIC = 8 μg/mL) and (MIC = 15 μg/mL), and antiproliferative activity against several human cancer cell lines (IC = 5.6-19.4 μM).
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http://dx.doi.org/10.1021/acs.jnatprod.1c00703DOI Listing
December 2021

Antibacterial Meroterpenoids, Merochlorins G-J from the Marine Bacterium sp.

Mar Drugs 2021 Oct 30;19(11). Epub 2021 Oct 30.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093-0204, USA.

Four new chlorinated meroterpenoids, merochlorins G-J (-), and , a dihydronaphthalenedione precursor, along with known merochlorins A () and C-F (-), were obtained from cultivation of the bacterium strain sp. CNH-189, which was isolated from marine sediment. The planar structures of compounds - and were elucidated by interpretation of MS, UV, and NMR spectroscopic data. The relative configurations of compounds - were determined via analysis of nuclear Overhauser effect (NOE) spectroscopic data, after which their absolute configurations were established by comparing the experimental electronic circular dichroism (ECD) spectra of compounds - to those of previously reported possible enantiomer models and DP4 calculations. Compound displayed strong antibacterial activities against , , and , with MIC values of 1, 2, and 2 μg/mL, respectively, whereas compound exhibited weak antibacterial effects on these three strains, with a 16-32 μg/mL MIC value range.
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http://dx.doi.org/10.3390/md19110618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624273PMC
October 2021

Pseudoalteromone A, a Ubiquinone Derivative from Marine spp., Suppresses Melanogenesis.

Mar Drugs 2021 Oct 28;19(11). Epub 2021 Oct 28.

Basic Research & Innovation Division, Amorepacific R&D Unit, Yongin 17074, Korea.

An ubiquinone derivative, pseudoalteromone A (), has been isolated from two marine-derived spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.
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http://dx.doi.org/10.3390/md19110612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618130PMC
October 2021

Potent and Selective Inhibitors of Human Monoamine Oxidase A from an Endogenous Lichen Fungus .

J Fungi (Basel) 2021 Oct 18;7(10). Epub 2021 Oct 18.

Department of Pharmacy, Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

Using 126 endogenous lichen fungus (ELF) extracts, inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) were evaluated. Among them, extract ELF29 of the endogenous fungus of the lichen showed the highest inhibitory activity against hMAO-A. Compounds alternariol (AT), 5'-hydroxy-alternariol (HAT), and mycoepoxydiene (MED), isolated from the extract, had potent inhibitory activities against hMAO-A with IC values of 0.020, 0.31, and 8.68 µM, respectively. AT, HAT, and MED are reversible competitive inhibitors of hMAO-A with K values of 0.0075, 0.116, and 3.76 µM, respectively. The molecular docking studies suggested that AT, HAT, and MED had higher binding affinities for hMAO-A (-9.1, -6.9, and -5.6 kcal/mol, respectively) than for hMAO-B (-6.3, -5.2, and -3.7 kcal/mol, respectively). The relative tight binding might result from a hydrogen bond interaction of the three compounds with a Tyr444 residue in hMAO-A, whereas no hydrogen bond interaction was proposed in hMAO-B. In silico pharmacokinetics, the three compounds showed high gastrointestinal absorption without violating Lipinski's five rules, but only MED showed high probability to cross the blood-brain barrier. These results suggest that AT, HAT, and MED are candidates for treating neuropsychiatric disorders, such as depression and cardiovascular disease.
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http://dx.doi.org/10.3390/jof7100876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541017PMC
October 2021

Antibacterial Bicyclic Fatty Acids from a Korean Colonial Tunicate sp.

Mar Drugs 2021 Sep 16;19(9). Epub 2021 Sep 16.

Laboratory of Marine Drugs, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul 08826, Korea.

Five new bicyclic carboxylic acids were obtained by antibacterial activity-guided isolation from a Korean colonial tunicate sp. Their structures were elucidated by the interpretation of NMR, MS and CD spectroscopic data. They all belong to the class of aplidic acids. Three of them were amide derivatives (-), and the other two were dicarboxylic derivatives ( and ). The absolute configurations were determined by a bisignate pattern of CD spectroscopy, which revealed that the absolute configurations of amides were opposite to those of dicarboxylates at every stereogenic centers. Compound exhibited the most potent antibacterial activity (MIC, 2 μg/mL).
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http://dx.doi.org/10.3390/md19090521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465582PMC
September 2021

Acremonamide, a Cyclic Pentadepsipeptide with Wound-Healing Properties Isolated from a Marine-Derived Fungus of the Genus .

J Nat Prod 2021 08 13;84(8):2249-2255. Epub 2021 Aug 13.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, United States.

Acremonamide () was isolated from a marine-derived fungus belonging to the genus . The chemical structure of was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide () was found to contain -Me-Phe, -Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino acids were determined through acid hydrolysis followed by the advanced Marfey's method, whereas the absolute configuration of 2-hydroxyisovaleric acid was determined through GC-MS analysis after formation of the -pentafluoropropionylated derivative of the (-)-menthyl ester of 2-hydroxyisovaleric acid. As an intrinsic biological activity, acremonamide () did not exert cytotoxicity to cancer and noncancer cells and increased the migration and invasion. Based on these activities, the wound healing properties of acremonamide () were confirmed and .
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http://dx.doi.org/10.1021/acs.jnatprod.1c00305DOI Listing
August 2021

Chromenone Derivatives as Monoamine Oxidase Inhibitors from Marine-Derived MAR4 Clade sp. CNQ-031.

J Microbiol Biotechnol 2021 Jul;31(7):1022-1027

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea.

Three compounds were isolated from marine-derived sp. CNQ-031, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase (BACE-1) were evaluated. Compound 1 (5,7-dihydroxy-2-isopropyl-4H-chromen-4-one) was a potent and selective inhibitor of MAO-A, with a 50% inhibitory concentration (IC) of 2.70 μM and a selectivity index (SI) of 10.0 versus MAO-B. Compound 2 [5,7-dihydroxy-2-(1-methylpropyl)-4H-chromen-4-one] was a potent and low-selective inhibitor of MAO-B, with an IC of 3.42 μM and an SI value of 2.02 versus MAO-A. Compound 3 (1-methoxyphenazine) did not inhibit MAO-A or MAO-B. All three compounds showed little inhibitory activity against AChE, BChE, and BACE-1. The K value of compound 1 for MAO-A was 0.94 ± 0.28 μM, and the K values of compound 2 for MAO-A and MAO-B were 3.57 ± 0.60 and 1.89 ± 0.014 μM, respectively, with competitive inhibition. The 1-methylpropyl group in compound 2 increased the MAO-B inhibitory activity compared with the isopropyl group in compound 1. Inhibition of MAO-A and MAO-B by compounds 1 and 2 was recovered by dialysis experiments. These results suggest that compounds 1 and 2 are reversible, competitive inhibitors of MAOs and can be considered potential therapies for neurological disorders such as depression and Alzheimer's disease.
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http://dx.doi.org/10.4014/jmb.2105.05003DOI Listing
July 2021

Antioxidative and anti-inflammatory activity of psiguadial B and its halogenated analogues as potential neuroprotective agents.

Bioorg Chem 2021 08 26;113:105027. Epub 2021 May 26.

New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea. Electronic address:

Psiguadial B (8), and its fluoro- (8a), chloro- (8b), and bromo- (8c) derivatives were synthesized using a sodium acetate-catalyzed single step coupling of three components: β-caryophyllene (5), diformylphloroglucinol (11), and benzaldehyde (12). These compounds efficiently and dose-dependently decreased HO-induced cell death, a quantitative marker of cell death, in primary cultures of mouse cortical neurons. Psiguadial B also decreased neuronal death and accumulation of ROS induced by FeCl in cortical cultures. The in vitro effects of these compounds in lipopolysaccharide (LPS)-induced expression of nitric oxide (NO), and TNF-α and IL-6 by suppressing the NF-κB pathway in immune cells demonstrated their antioxidative and anti-inflammatory activity. The present findings warrant further research on the development of psiguadial B-based neuroprotective agents for the treatment of neurodegenerative diseases, acute brain injuries and immunological disorders.
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http://dx.doi.org/10.1016/j.bioorg.2021.105027DOI Listing
August 2021

Azetidine-Bearing Non-Ribosomal Peptides, Bonnevillamides D and E, Isolated from a Carrion Beetle-Associated Actinomycete.

J Org Chem 2021 08 12;86(16):11149-11159. Epub 2021 May 12.

Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Two new nonribosomal peptides, bonnevillamides D and E ( and ), have been discovered in sp. UTZ13 isolated from the carrion beetle, . Combinational analysis of the UV, MS, and NMR spectroscopic data revealed that their planar structures were comprised of dichlorinated linear peptides containing nonproteinogenic amino acid residues, such as 4-methylazetidinecarboxylic acid and 4--acetyl-5-methylproline. The configurations of bonnevillamides D and E ( and ) were determined based on ROESY correlations, the advanced Marfey's method, phenylglycine methyl ester derivatization, molecular modeling, and circular dichroism spectroscopy. The nonribosomal peptide synthetase biosynthetic pathway of bonnevillamides D and E has been proposed using bioinformatic analysis of the whole-genome sequence data of sp. UTZ13. Their biological activity toward the aggregation of amyloid-β, which is one of the key pathogenic proteins in Alzheimer's disease, was evaluated using a thioflavin T assay and gel electrophoresis. Bonnevillamides D and E reversed the fibril formation by inducing the monomerization of amyloid-β aggregates.
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http://dx.doi.org/10.1021/acs.joc.1c00360DOI Listing
August 2021

Chemical Structure and Biological Activities of Secondary Metabolites from L.

Molecules 2021 Apr 13;26(8). Epub 2021 Apr 13.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.

L. is a halophyte that grows in salt marshes and muddy seashores, which is widely used both as traditional medicine and as an edible vegetable. This salt-tolerant plant is a source of diverse secondary metabolites with several therapeutic properties, including antioxidant, antidiabetic, cytotoxic, anti-inflammatory, and anti-obesity effects. Therefore, this review summarizes the chemical structure and biological activities of secondary metabolites isolated from L.
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http://dx.doi.org/10.3390/molecules26082252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069253PMC
April 2021

Svalbamides A and B, Pyrrolidinone-Bearing Lipodipeptides from Arctic sp.

Mar Drugs 2021 Apr 17;19(4). Epub 2021 Apr 17.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Korea.

Two new secondary metabolites, svalbamides A () and B (), were isolated from a culture extract of sp. SVB7 that was isolated from surface sediment from a core (HH17-1085) taken in the Svalbard archipelago in the Arctic Ocean. The combinational analysis of HR-MS and NMR spectroscopic data revealed the structures of and as being lipopeptides bearing 3-amino-2-pyrrolidinone, d-valine, and 3-hydroxy-8-methyldecanoic acid. The absolute configurations of the amino acid residues in svalbamides A and B were determined using the advanced Marfey's method, in which the hydrolysates of and were derivatized with l- and d- forms of 1-fluoro-2,4-dinitrophenyl-5-alanine amide (FDAA). The absolute configurations of and were completely assigned by deducing the stereochemistry of 3-hydroxy-8-methyldecanoic acid based on DP4 calculations. Svalbamides A and B induced quinone reductase activity in Hepa1c1c7 murine hepatoma cells, indicating that they represent chemotypes with a potential for functioning as chemopreventive agents.
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http://dx.doi.org/10.3390/md19040229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073366PMC
April 2021

Dumulmycin, an Antitubercular Bicyclic Macrolide from a Riverine Sediment-Derived sp.

Org Lett 2021 05 22;23(9):3359-3363. Epub 2021 Apr 22.

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.

Dumulmycin () was isolated from sp. DM28, a bacterial strain from a riverine sediment sample. The structure of was elucidated as a bicyclic macrolide possessing 19-membered and 5-membered rings by spectroscopic analysis. The stereochemistry of was determined by -based configuration analysis, ROESY NMR data, DP4 calculations, and the modified Mosher's method. Genetic analysis identified a -acyltransferase polyketide biosynthetic gene cluster for . Dumulmycin exhibited antitubercular activity (MIC = 27.1 μM).
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http://dx.doi.org/10.1021/acs.orglett.1c00847DOI Listing
May 2021

Selective Inhibition of Human Monoamine Oxidase B by 5-hydroxy-2-methyl-chroman-4-one Isolated from an Endogenous Lichen Fungus .

J Fungi (Basel) 2021 Jan 26;7(2). Epub 2021 Jan 26.

Department of Pharmacy, and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Korea.

Inhibitory activities against monoamine oxidases (MAOs) and cholinesterases (ChEs) and antioxidant activity were evaluated for 195 extracts from Ukraine-derived endogenous lichen fungi (ELF). Among them, an ELF13 (identified as ) extract showed the highest inhibitory activity against MAO-B, and 5-hydroxy-2-methyl-chroman-4-one (HMC) was isolated as a ~ 4-fold selective inhibitor of MAO-B (IC = 3.23 µM) compared to MAO-A (IC = 13.97 µM). HMC is a reversible competitive inhibitor with a K value of 0.896 µM. No cytotoxicity was observed in normal and cancer cells at 50 µM of HMC. HMC showed blood-brain barrier permeability and high gastrointestinal absorption in silico pharmacokinetics. The docking simulation results showed that the binding affinity of HMC for MAO-B (-7.3 kcal/mol) was higher than that of MAO-A (-6.1 kcal/mol) and that HMC formed a hydrogen bond interaction with Cys172 of MAO-B (distance: 3.656 Å), whereas no hydrogen bonding was predicted with MAO-A. These results suggest that HMC can be considered a candidate for the treatment of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.
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http://dx.doi.org/10.3390/jof7020084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911959PMC
January 2021

Acremonidin E produced by sp. SNF123, a fungal endophyte of , has antimelanogenic activities.

J Ginseng Res 2021 Jan 21;45(1):98-107. Epub 2019 Nov 21.

College of Pharmacy, Ewha Womans University, Seoul, Republic of Korea.

Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Meyer.

Methods: An endophytic fungus, sp. SNF123 was isolated from the root of from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm.

Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT-PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue.

Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with for cosmetic ingredients.
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http://dx.doi.org/10.1016/j.jgr.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790906PMC
January 2021

Discrimination of and Based on Metabolite Analysis and Hepatoprotective Activity.

Molecules 2020 Dec 10;25(24). Epub 2020 Dec 10.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.

Lycii Fructus is a traditional medicine used to prevent liver and kidney diseases, which commonly derives from and . Here, the extracts and ethyl acetate-soluble fractions of fruits exhibited better hepatoprotective effects than those of , which was likely due to differences in their composition. Therefore, GC-MS and HPLC analyses were conducted to characterize the metabolite differences between and . Based on amino acid (AA) and phenolic acid (PA) profiling, 24 AAs and 9 PAs were identified in the two species. Moreover, each species exhibited unique and readily distinguishable AA and PA star graphic patterns. HPLC analysis elucidated composition differences between the ethyl acetate-soluble layers of the two compounds. Further, NMR analysis identified their chemical structures as 4-(2-formyl-5-(hydroxymethyl)-1-pyrrol-1-yl)butanoic acid and -coumaric acid. The higher content of 4-(2-formyl-5-(hydroxymethyl)-1-pyrrol-1-yl)butanoic acid was detected in , whereas the content of -coumaric acid was higher in . Therefore, the differences in the relative contents of these two secondary metabolites in the ethyl acetate-soluble layer of Lycii Fructus could be a good marker to discriminate between and .
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http://dx.doi.org/10.3390/molecules25245835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764731PMC
December 2020

Bioactive natural products from the genus Salinospora: a review.

Arch Pharm Res 2020 Dec 25;43(12):1230-1258. Epub 2020 Nov 25.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Korea.

Actinomycetes are an important source for bioactive secondary metabolites. Among them, the genus Salinispora is one of the first salt obligatory marine species worldwide and is typically found in various types of substrates in tropical and subtropical marine environments including sediments and marine organisms. This genus produces a wide range of chemical scaffolds and bioactive compounds such as lomaiviticins, cyclomarins, rifamycins, salinaphthoquinones, and salinosporamides. This review arranged Salinispora derived secondary metabolites according to the three species that comprise the genus. Moreover, muta- and semi-synthesis analogs derived from salinosporamide were also described in this review.
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http://dx.doi.org/10.1007/s12272-020-01288-1DOI Listing
December 2020

Colletotrichalactones A-Ca, unusual 5/6/10-fused tricyclic polyketides produced by an endophytic fungus, Colletotrichum sp. JS-0361.

Bioorg Chem 2020 12 3;105:104449. Epub 2020 Nov 3.

College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea. Electronic address:

Three unusual polyketides with a 5/6/10-fused ring system, named colletotrichalactones A-Ca (1-3a), were isolated from cultures of the endophytic fungus, Colletotrichum sp. JS-0361, which was isolated from a leaf of Morus alba. Their structures, including their absolute stereochemistries, were completely established using extensive spectroscopic methods together with a chemical reaction utilizing competing enantioselective acylation coupled with LC/MS. Compounds possessing this ring skeleton were previously reported in three studies. Our rigorous chemical investigation revealed the complete configuration of this skeleton, which agreed with the results for glabramycin B with this ring skeleton established by computational chemistry and enantioselective synthesis in previous reports. 1 and 2 had unstable aldehyde groups that were easily converted to acetal groups in the presence of solvents. Meanwhile, compound 3a, with terminal acetal functionality, was deduced to be an artefact originating from compound 3 with a terminal aldehyde group. Compounds 1 and 3a displayed moderate-to-potent cytotoxic activities against MCF7 cells with ICs of 35.06 and 25.20 µM, respectively.
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http://dx.doi.org/10.1016/j.bioorg.2020.104449DOI Listing
December 2020

Antaroide, a Novel Natural Nine-Membered Macrolide, Inhibits Melanin Biosynthesis in B16F10 Murine Melanoma Cells.

Biomol Ther (Seoul) 2021 Jan;29(1):98-103

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.

1: ). The chemical structure was established through the interpretation of MS, UV, and NMR spectroscopic data. Antaroide is a nine-membered macrolide with lactone and lactam moieties. To investigate its applicability in skin whitening cosmetics, its anti-melanogenic activity in B16F10 murine melanoma cells was examined. As a result, antaroide displayed strong inhibitory activities against melanin synthesis and also attenuated the dendrite formation induced by the α-melanocyte stimulating hormone (α-MSH). Antaroide suppressed the mRNA expression of the melanogenic enzymes such as tyrosinase, TRP-1 and TRP-2. This suggests that it may serve as a transcriptional regulator of melanogenesis. Collectively, the discovery of this novel natural nine-membered macrolide and its anti-melanogenic activity could give new insights for the development of skin whitening agents.
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http://dx.doi.org/10.4062/biomolther.2020.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771842PMC
January 2021

Androsamide, a Cyclic Tetrapeptide from a Marine sp., Suppresses Motility of Colorectal Cancer Cells.

J Nat Prod 2020 10 28;83(10):3166-3172. Epub 2020 Sep 28.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California-San Diego, La Jolla, California 92093-0204, United States.

A cyclic tetrapeptide, androsamide (), was isolated from a marine actinomycete of the genus , strain CNT-189. The planar structure of was assigned by the interpretation of 1D and 2D NMR spectroscopic data. The absolute configurations of constituent amino acids of were determined by application of the Marfey's and advanced Marfey's methods. Androsamide () strongly suppressed the motility of Caco2 cells caused by epithelial-mesenchymal transition.
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http://dx.doi.org/10.1021/acs.jnatprod.0c00815DOI Listing
October 2020

Sarmentosamide, an Anti-Aging Compound from a Marine-Derived sp. APmarine042.

Mar Drugs 2020 Sep 10;18(9). Epub 2020 Sep 10.

Amorepacific Corporation R&D Center, Yongin 17074, Korea.

Many bioactive materials have been isolated from marine microorganisms, including alkaloids, peptides, lipids, mycosporine-like amino acids, glycosides, and isoprenoids. Some of these compounds have great potential in the cosmetic industry due to their photo-protective, anti-aging, and anti-oxidant activities. In this study, sarmentosamide () was isolated from marine-derived sp. APmarine042, after which its capacity to decrease skin aging was examined in-vitro. Sarmentosamide () was found to significantly reduce UVB-induced matrix metalloproteinase-1 (MMP-1) expression in normal human dermal fibroblasts (NHDFs) by inhibiting the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) phosphorylation, which are regulatory pathways upstream of MMP-1 transcription. Additionally, we confirmed that sarmentosamide () decreased tumor necrosis factor-alpha (TNF-α), induced MMP-1 secretion in NHDFs, and exhibited free-radical scavenging activity, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Therefore, our study suggests that sarmentosamide () could be a promising anti-aging agent that acts via the downregulation of MMP-1 expression.
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http://dx.doi.org/10.3390/md18090463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551700PMC
September 2020

Marine natural products with monoamine oxidase (MAO) inhibitory activity.

Pharm Biol 2020 Dec;58(1):716-720

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Republic of Korea.

Context: Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products.

Objective: To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO.

Methods: Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine.

Results: Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources.

Conclusions: This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.
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http://dx.doi.org/10.1080/13880209.2020.1790618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470022PMC
December 2020

Two new secondary metabolites, saccharochlorines A and B, from a marine bacterium Saccharomonospora sp. KCTC-19160.

Bioorg Med Chem Lett 2020 06 29;30(11):127145. Epub 2020 Mar 29.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea. Electronic address:

Two new chlorinated secondary metabolites, saccharochlorines A and B (1 and 2), were isolated from the saline cultivation of a marine-derived bacterium Saccharomonospora sp. (KCTC-19160). The chemical structures of the saccharochlorines were elucidated by 2D NMR and MS spectroscopic data. Saccharochlorines A and B (1 and 2) exhibit weak inhibition of β-secretase (BACE1) in biochemical inhibitory assay, but they induced the release of Aβ (1-40) and Aβ (1-42) in H4-APP neuroglial cells. This discrepancy might be derived from the differences between the cellular and sub-cellular environments or the epigenetic stimulation of BACE1 expression.
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http://dx.doi.org/10.1016/j.bmcl.2020.127145DOI Listing
June 2020

An Activatable AIEgen Probe for High-Fidelity Monitoring of Overexpressed Tumor Enzyme Activity and Its Application to Surgical Tumor Excision.

Angew Chem Int Ed Engl 2020 06 10;59(25):10186-10195. Epub 2020 Mar 10.

Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, 03760, Korea.

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM-ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline-malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP-recognition units. The rapid liberation of DQM-OH aggregates in the presence of ALP resulted in aggregation-induced fluorescence. The up-regulation of ALP expression in tumor cells was imaged using DQM-ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two-photon microscopy platform, providing the fluorescence-guided recognition of sub-millimeter tumorigenesis. DQM-ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.
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http://dx.doi.org/10.1002/anie.202001675DOI Listing
June 2020

Salvianolic Acid B Inhibits Hand-Foot-Mouth Disease Enterovirus 71 Replication through Enhancement of AKT Signaling Pathway.

J Microbiol Biotechnol 2020 Jan;30(1):38-43

Department of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk 28024, Republic of Korea.

Hand, foot, and mouth disease (HFMD) is caused by enterovirus 71 (EV71) in infants and children under six years of age. HFMD is characterized by fever, mouth ulcers, and vesicular rashes on the palms and feet. EV71 also causes severe neurological manifestations, such as brainstem encephalitis and aseptic meningitis. Recently, frequent outbreaks of EV71 have occurred in the Asia-Pacific region, but currently, no effective antiviral drugs have been developed to treat the disease. In this study, we investigated the antiviral effect of salvianolic acid B (SalB) on EV71. SalB is a major component of the root and has been shown to be an effective treatment for subarachnoid hemorrhages and myocardial infarctions. HeLa cells were cultured in 12-well plates and treated with SalB (100 or 10 µg/ml) and 10 PFU/ml of EV71. SalB treatment (100 µg/ml) significantly decreased the cleavage of the eukaryotic eIF4G1 protein and reduced the expression of the EV71 capsid protein VP1. In addition, SalB treatment showed a dramatic decrease in viral infection, measured by immunofluorescence staining. The Akt signaling pathway, a key component of cell survival and proliferation, was significantly increased in EV71-infected HeLa cells treated with 100 µg/ml SalB. RT-PCR results showed that the mRNA for anti-apoptotic protein Bcl-2 and the cell cycle regulator Cyclin-D1 were significantly increased by SalB treatment. These results indicate that SalB activates Akt/PKB signaling and inhibits apoptosis in infected HeLa cells. Taken together, these results suggest that SalB could be used to develop a new therapeutic drug for EV71-induced HFMD.
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http://dx.doi.org/10.4014/jmb.1907.07079DOI Listing
January 2020

Neuroprotective Glycosylated Cyclic Lipodepsipeptides, Colletotrichamides A-E, from a Halophyte-Associated Fungus, JS419.

J Org Chem 2019 09 20;84(17):10999-11006. Epub 2019 Aug 20.

College of Pharmacy , Duksung Women's University , Seoul 01369 , South Korea.

Glutamate neurotoxicity has been implicated in neuronal death in both acute CNS injury and in chronic neurodegenerative diseases. Five unique cyclic depsipeptides with neuroprotective activity, colletotrichamides A-E (-), were isolated from cultures of a halophyte -associated fungus, JS419. Spectroscopic analysis revealed that they were glycosylated cyclic lipodepsipeptides. Their relative configurations were determined by ROESY and -based configuration analysis, and absolute configurations were established by chemical reactions including modified Mosher's method, advanced Marfey's method, and sugar derivatization. This is the first report of a glycosylated dimethyl-trioxygenated dodecanoyl moiety, and the relative as well as absolute stereochemistry was elucidated herein for the first time. Colletotrichamide C exhibited strong neuroprotective activity against glutamate in hippocampal HT22 cells.
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http://dx.doi.org/10.1021/acs.joc.9b01511DOI Listing
September 2019

Mycousfurans A and B, Antibacterial Usnic Acid Congeners from the Fungus sp., Isolated from a Marine Sediment.

Mar Drugs 2019 Jul 19;17(7). Epub 2019 Jul 19.

Laboratory of Marine Drugs, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul 08826, Korea.

Mycousfurans ( and ), two new usnic acid congeners, along with (-)-mycousnine (), (-)-placodiolic acid (), and (+)-usnic acid (), were isolated using high-performance liquid chromatography-ultraviolet (HPLC-UV)-guided fractionation of extracts of sp. isolated from a marine sediment. The planar structures of and were elucidated using 1D and 2D NMR spectra. The relative configurations of the stereogenic carbons of and were established via analysis of their nuclear Overhauser spectroscopy (NOESY) spectra, and their absolute configurations were determined using a comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds and were found to have antibacterial activity, showing moderate activity against and .
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http://dx.doi.org/10.3390/md17070422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669435PMC
July 2019

Biosynthesis of Nonimmunosuppressive FK506 Analogues with Antifungal Activity.

J Nat Prod 2019 08 19;82(8):2078-2086. Epub 2019 Jul 19.

Department of Chemistry and Nanoscience , Ewha Womans University , Seoul 03760 , Republic of Korea.

A reduction in the strong immunosuppressive activity of FK506 () is essential for developing this compound as an antifungal agent. Seven new FK506 analogues modified at both the FK506-binding protein 12- and the calcineurin-binding regions were biosynthesized. 9-DeoxoFK520 () exhibited a >900-fold reduction in the immunosuppressive activity but maintained significant antifungal activity, indicating that the C-9 and C-21 positions are critical for separation of immunosuppressive and antifungal activities. exhibited robust synergistic antifungal activity with fluconazole. FK506 () is a 23-membered macrolide produced by several species and is used as an immunosuppressive drug to prevent the rejection of transplanted organs. FK506 has also exhibited antifungal, neuroprotective, and neuroregenerative activities. In humans, FK506 binds to FK506-binding protein (FKBP) 12, and the resulting FKBP12-FK506 complex interacts with a Ca-calmodulin-dependent phosphatase, calcineurin (CaN). Inactivation of CaN by forming the FKBP12-FK506-CaN ternary complex prevents the activation of nuclear factor of activated T cells (NF-AT), inhibiting the production of interleukin-2 and subsequent T-cell proliferation. This CaN signaling pathway also plays a critical role in the growth and pathogenesis of major fungal pathogens such as , , and . Therefore, the synthesis of FK506 analogues that can discriminate human FKBP12/CaN from its fungal counterparts may separate antifungal activity from the immunosuppressive activity, thereby allowing the development of a novel antifungal agent.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00144DOI Listing
August 2019

Meroindenon and Merochlorins E and F, Antibacterial Meroterpenoids from a Marine-Derived Sediment Bacterium of the Genus .

Org Lett 2019 08 12;21(15):5779-5783. Epub 2019 Jul 12.

Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography , University of California San Diego , La Jolla , California 92093-0204 , United States.

Meroterpenoids, meroindenon () and merochlorins E () and F (), were isolated from a marine-derived bacterium belonging to the genus . Their chemical structures were established using extensive analysis of MS, UV, ECD, and NMR spectroscopic data. Compounds - possess a tetrahydroxynaphthalene core and a C-isoprene unit. Compounds and exhibited strong antibacterial activities against , , and , with a range of MIC values from 1 to 2 μg/mL.
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http://dx.doi.org/10.1021/acs.orglett.9b01440DOI Listing
August 2019
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