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  1. Article ; Online: Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

    Till Steinmetz / Blaise Kimbadi Lombe / Markus Nett

    Beilstein Journal of Organic Chemistry, Vol 19, Iss 1, Pp 909-

    2023  Volume 917

    Abstract: Siderophores are small molecules secreted by microorganisms in order to scavenge iron from the environment. An example is the thiazoline-containing natural product massiliachelin, which is produced by Massilia sp. NR 4-1 under iron-deficient conditions. ... ...

    Abstract Siderophores are small molecules secreted by microorganisms in order to scavenge iron from the environment. An example is the thiazoline-containing natural product massiliachelin, which is produced by Massilia sp. NR 4-1 under iron-deficient conditions. Based on experimental evidence and genome analysis, it was suspected that this bacterium synthesizes further iron-chelating molecules. After a thorough inspection of its metabolic profile, six previously overlooked compounds were isolated that were active in the chrome azurol S (CAS) assay. Mass spectrometric measurements and nuclear magnetic resonance spectroscopic analyses identified these compounds as possible biosynthetic intermediates or shunt products of massiliachelin. Their bioactivity was tested against one Gram-positive and three Gram-negative bacteria.
    Keywords massilia ; massiliachelin ; siderophore ; structure elucidation ; Science ; Q ; Organic chemistry ; QD241-441
    Subject code 540
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Beilstein-Institut
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article: Ancistrolikokine E₃, a 5,8′-Coupled Naphthylisoquinoline Alkaloid, Eliminates the Tolerance of Cancer Cells to Nutrition Starvation by Inhibition of the Akt/mTOR/Autophagy Signaling Pathway

    Awale, Suresh / Dya Fita Dibwe / Chandrasekar Balachandran / Shaimaa Fayez / Doris Feineis / Blaise Kimbadi Lombe / Gerhard Bringmann

    Journal of natural products. 2018 Oct. 10, v. 81, no. 10

    2018  

    Abstract: PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity ... ...

    Abstract PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells during a limited supply of nutrients and oxygen. The new 5,8′-coupled naphthyldihydroisoquinoline alkaloid ancistrolikokine E₃ (4), isolated from the Congolese liana Ancistrocladus likoko, showed potent preferential cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC₅₀ value of 2.5 μM, without exhibiting toxicity in normal, nutrient-rich medium. The compound was found to induce dramatic alterations in cell morphology, leading to cell death. Moreover, it inhibited significantly PANC-1 cell migration and colony formation in a concentration-dependent manner. This study on 4 provides the first live evidence of the effect of a naphthyldihydroisoquinoline alkaloid against PANC-1 cells in nutrient-deprived medium. Mechanistic investigations conducted suggest that compound 4 is a potent inhibitor of the activation of the Akt/mTOR pathway. Furthermore, it inhibited the expression levels of the key autophagy regulators Atg5, Atg12, Beclin-1, LC3-I, and LC3-II. The results demonstrated that ancistrolikokine E₃ (4) is a potent early-stage inhibitor of the autophagy pathway in PANC-1 human pancreatic cancer cells. Ancistrolikokine E₃ (4) and related naphthylisoquinoline alkaloids are promising potential lead compounds for anticancer drug development based on the antiausterity strategy.
    Keywords Ancistrocladus ; alkaloids ; anaerobic conditions ; antineoplastic agents ; autophagy ; cell movement ; cytotoxicity ; humans ; neoplasm cells ; nutrients ; oxygen ; pancreatic neoplasms ; signal transduction ; starvation
    Language English
    Dates of publication 2018-1010
    Size p. 2282-2291.
    Publishing place American Chemical Society and American Society of Pharmacognosy
    Document type Article
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.8b00733
    Database NAL-Catalogue (AGRICOLA)

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