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Tytuł:
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Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways.
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Autorzy:
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Jouda JB; Department of Chemical Engineering, School of Chemical Engineering and Mineral Industries, University of Ngaoundere, Ngaoundere, Cameroon.
Njoya EM; Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.; Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
Fobofou SAT; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, USA.
Zhou ZY; Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
Qiang Z; Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
Mbazoa CD; Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
Brandt W; Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle (Saale), Germany.
Zhang GL; Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
Wandji J; Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon.
Wang F; Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.
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Źródło:
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Planta medica [Planta Med] 2020 Sep; Vol. 86 (13-14), pp. 1032-1042. Date of Electronic Publication: 2020 Aug 05.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Stuttgart ; New York : George Thieme
Original Publication: Stuttgart, Hippokrates Verlag.
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MeSH Terms:
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Polyketides/*pharmacology
Animals ; Cyclooxygenase 2 ; Lipopolysaccharides ; MAP Kinase Signaling System ; Mice ; NF-KappaB Inhibitor alpha ; NF-kappa B ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Signal Transduction
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Grant Information:
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National Natural Science Foundation of China 21861142007; Bundesministerium für Bildung und Forschung 100318210; Deutscher Akademischer Austauschdienst 57316173; Deutscher Akademischer Austauschdienst 573169155; Deutscher Akademischer Austauschdienst A/12/90548; Chinese Academy of Sciences President's International Fellowship Initiative 2015PB049; Biological Resource Network of Chinese Academy of Sciences ZSTH-030
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Substance Nomenclature:
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0 (Lipopolysaccharides)
0 (NF-kappa B)
0 (Polyketides)
139874-52-5 (NF-KappaB Inhibitor alpha)
31C4KY9ESH (Nitric Oxide)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.99.1 (Cyclooxygenase 2)
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Entry Date(s):
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Date Created: 20200807 Date Completed: 20200925 Latest Revision: 20200925
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Update Code:
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20240105
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DOI:
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10.1055/a-1212-2930
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PMID:
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32757200
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Three previously undescribed natural products, phomopsinin A - C (1: - 3: ), together with three known compounds, namely, cis -hydroxymellein (4: ), phomoxanthone A (5: ) and cytochalasin L-696,474 (6: ), were isolated from the solid culture of Phomopsis sp. CAM212, an endophytic fungus obtained from Garcinia xanthochymus . Their structures were determined on the basis of spectroscopic data, including IR, NMR, and MS. The absolute configurations of 1: and 2: were assigned by comparing their experimental and calculated ECD spectra. Acetylation of compound 1: yielded 1A: , a new natural product derivative that was tested together with other isolated compounds on lipopolysaccharide-stimulated RAW 264.7 cells. Cytochalasin L-696,474 (6: ) was found to significantly inhibit nitric oxide production, but was highly cytotoxic to the treated cells, whereas compound 1: slightly inhibited nitric oxide production, which was not significantly different compared to lipopolysaccharide-treated cells. Remarkably, the acetylated derivative of 1: , compound 1A: , significantly inhibited nitric oxide production with an IC 50 value of 14.8 µM and no cytotoxic effect on treated cells, thereby showing the importance of the acetyl group in the anti-inflammatory activity of 1A: . The study of the mechanism of action revealed that 1A: decreases the expression of inducible nitric oxide synthase, cyclooxygenase 2, and proinflammatory cytokine IL-6 without an effect on IL-1 β expression. Moreover, it was found that 1A: exerts its anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells by downregulating the activation of ERK1/2 and by preventing the translocation of nuclear factor κ B. Thus, derivatives of phomopsinin A (1: ), such as compound 1A: , could provide new anti-inflammatory leads.
Competing Interests: The authors declare that they have no conflict of interest.
(Thieme. All rights reserved.)
