31 research outputs found

    Design and Synthesis of Novel Lamellarin D Analogues Targeting Topoisomerase I

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    ナノダイナミクス国際シンポジウム 平成22年1月21日(木) 於長崎大学Nagasaki Symposium on Nano-Dynamics 2010 (NSND2010), January 21, 2010, Nagasaki University, Nagasaki, Japan, Invited Lectur

    Efficient Total Syntheses of Heterocyclic Marine Alkaloids, Lamellarins

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    Nagasaki Symposium on Nano-Dynamics 2008 (NSND2008) 平成20年1月29日(火)於長崎大学 Poster Presentatio

    Total synthesis of the marine natural products lukianols A and B

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    Total synthesis of the pyrrolic marine natural products lukianols A (1) and B (2) has been achieved using N-benzenesulfonyl-3,4-dibromopyrrole (3) as a common starting material. The key synthetic strategy developed is the combined bromine-directed lithiation and palladium-catalyzed cross-coupling of 3 to produce 3,4-diarylpyrrol-2-carboxylates. Regioselective iodination of the phenolic intermediate 24 was thoroughly investigated for the synthesis of lukianol B

    Unique Mode of Antiviral Action of a Marine Alkaloid against Ebola Virus and SARS-CoV-2.

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    Lamellarin α 20-sulfate is a cell-impenetrable marine alkaloid that can suppress infection that is mediated by the envelope glycoprotein of human immunodeficiency virus type 1. We explored the antiviral action and mechanisms of this alkaloid against emerging enveloped RNA viruses that use endocytosis for infection. The alkaloid inhibited the infection of retroviral vectors that had been pseudotyped with the envelope glycoprotein of Ebola virus and SARS-CoV-2. The antiviral effects of lamellarin were independent of the retrovirus Gag-Pol proteins. Interestingly, although heparin and dextran sulfate suppressed the cell attachment of vector particles, lamellarin did not. In silico structural analyses of the trimeric glycoprotein of the Ebola virus disclosed that the principal lamellarin-binding site is confined to a previously unappreciated cavity near the NPC1-binding site and fusion loop, whereas those for heparin and dextran sulfate were dispersed across the attachment and fusion subunits of the glycoproteins. Notably, lamellarin binding to this cavity was augmented under conditions where the pH was 5.0. These results suggest that the final action of the alkaloid against Ebola virus is specific to events following endocytosis, possibly during conformational glycoprotein changes in the acidic environment of endosomes. Our findings highlight the unique biological and physicochemical features of lamellarin α 20-sulfate and should lead to the further use of broadly reactive antivirals to explore the structural mechanisms of virus replication

    Unique Mode of Antiviral Action of a Marine Alkaloid against Ebola Virus and SARS-CoV-2

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    Lamellarin α20-sulfate is a cell-impenetrable marine alkaloid that can suppress infection that is mediated by the envelope glycoprotein of human immunodeficiency virus type 1. We explored the antiviral action and mechanisms of this alkaloid against emerging enveloped RNA viruses that use endocytosis for infection. The alkaloid inhibited the infection of retroviral vectors that had been pseudotyped with the envelope glycoprotein of Ebola virus and SARS-CoV-2. The antiviral effects of lamellarin were independent of the retrovirus Gag-Pol proteins. Interestingly, although heparin and dextran sulfate suppressed the cell attachment of vector particles, lamellarin did not. In silico structural analyses of the trimeric glycoprotein of the Ebola virus disclosed that the principal lamellarin-binding site is confined to a previously unappreciated cavity near the NPC1-binding site and fusion loop, whereas those for heparin and dextran sulfate were dispersed across the attachment and fusion subunits of the glycoproteins. Notably, lamellarin binding to this cavity was augmented under conditions where the pH was 5.0. These results suggest that the final action of the alkaloid against Ebola virus is specific to events following endocytosis, possibly during conformational glycoprotein changes in the acidic environment of endosomes. Our findings highlight the unique biological and physicochemical features of lamellarin α20-sulfate and should lead to the further use of broadly reactive antivirals to explore the structural mechanisms of virus replication

    A formal total synthesis of the telomerase inhibitor dictyodendrin B

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    A formal synthesis of the telomerase inhibitory marine pyrrolocarbazole alkaloid dictyodendrin B is described. The key features are consecutive palladium-catalyzed cross-coupling reactions and intramolecular reductive coupling reaction to construct the pyrrolo[2,3-c]carbazole framework

    Synthesis, structure-activity relationships, and mechanism of action of anti-HIV-1 lamellarin α 20-sulfate analogues.

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    Lamellarin α and six different types of lamellarin α 20-sulfate analogues were synthesized and their structure-activity relationships were investigated using a single round HIV-1 vector infection assay. All lamellarin sulfates having pentacyclic lamellarin core exhibited anti-HIV-1 activity at a 10μM concentration range regardless of the number and position of the sulfate group. On the other hand, non-sulfated lamellarin α and ring-opened lamellarin sulfate analogues did not affect HIV-1 vector infection in similar concentrations. The lamellarin sulfates utilized in this study did not exhibit unfavorable cytotoxic effect under the concentrations tested (IC(50)>100μM). Confocal laser scanning microscopic analysis indicated that hydrophilic lamellarin sulfates were hardly incorporated in the cell. HIV-1 Env-mediated cell-cell fusion was suppressed by lamellarin sulfates. These results suggested that lamellarin sulfates have a novel anti-HIV-1 activity besides the previously reported integrase activity inhibition, possibly at a viral entry step of HIV-1 replication

    Algicidal activity of polyunsaturated fatty acids derived from Ulva fasciata and U. pertusa (Ulvaceae, Chlorophyta) on phytoplankton

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    Isolation of algicidal compounds from Ulva fasciata revealed that the algicidal substances were the polyunsaturated fatty acids (PUFAs) as hexadeca-4,7,10,13-tetraenoic acid (HDTA) C16:4 n-3, octadeca-6,9,12,15- tetraenoic acid (ODTA) C18:4 n-3, α-linolenic acid (ALA) C18:3 n-3 and linoleic acid (LA) C18:2 n-6. The fatty acid composition of four species of Ulvaceae (U. fasciata, U. pertusa, U. arasakii and U. conglobota) was analyzed by capillary gas chromatography to investigate the relationship with the algicidal activity. The results indicate that highly algicidal species, U. fasciata and U. pertusa, showed higher contents of C16:4 n-3, C18:3 n-3, and C18:4 n-3. Concentrations of these PUFAs released from the seaweed in the culture medium were also analyzed. These PUFAs were found to be significantly active against Chattonella antiqua, C. marina, Fibrocapsa japonica, Heterosigma akashiwo, Karenia mikimotoi, moderately effective against Heterocapsa circularisquama, Prorocentrum minimum, P. sigmoides, Scrippsiella trochoidea, whereas low effective against Alexandrium catenella and Cochlodinium polykrikoides. It is suggested that the PUFAs are useful mitigation agents to remove several harmful effects without causing detrimental effects on surrounding marine living organisms

    Synthesis and Biological Activity of Lamellarin Alkaloids: An Overview

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    Lamellarins are natural products isolated from marine invertebrates having a unique heterocyclic ring system. Many of these natural products exhibit potentially useful biological activities such as antitumor and anti-HIV activities. In this review, we summarized the synthesis and biological activity of naturally occurring lamellarins and their analogues

    Bioactivities of algicidal C18 hydroxy unsaturated fatty acid isolated from the red alga Tricleocarpa jejuensis and its synthesized propargylic derivative

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    (±)-(E)-12-hydroxyoctadec-10-enoic acid (compound A) was isolated from the red alga Tricleocarpa jejuensis in our previous study as a potent algicidal compound against red tide microalga Chattonella antiqua (Ochrophyta, Raphidophyceae). Interestingly, its propargylic derivative, 12-hydroxyoctadec-10-ynoic acid (compound B), which was obtained as a synthetic intermediate of compound A, showed an even more extensive algicidal activity. In this study, the effects of compound A and B on the major causative species of harmful algal blooms (HABs) such as Chattonella marina (Ochrophyta, Raphidophyceae), Heterocapsa circularisquama, and Karenia mikimotoi (Miozoa, Dinophyceae) in addition to C. antiqua were investigated. Both compounds exhibited toxic effects on these red tide flagellates in a concentration dependent manner with LC50 < 10 μg/mL, and the activities of compound B were much stronger than compound A. Zooplankton rotifer (Brachionys plicatilis) was relatively resistant to the compounds, and the lethal effects of H. circularisquama and K. mikimotoi on rotifers were reduced in the presence of compound A and B, suggesting their potential usage in the mitigation strategy for HABs. Consistent with the toxicities on the HAB species, compound B showed stronger cytotoxicity on HeLa, XC, and U937 cells than A. Since compound B but not compound A showed haemolytic activity on rabbit erythrocytes, specific action of compound B on cell membrane may be responsible for the potent cytotoxicity. Furthermore, compound B exhibited higher antibacterial effect on Staphylococcus aureus than compound A, while both were not effective on Enchiridia coli. Our results suggest that compound A and B are promising multifunctional candidates with potential to develop not only as anti-red tide microalgae but also as tumor cell-killing and antibacterial agents. This is the first report indicating that replacing a double bond in the hydroxy unsaturated fatty acid with a triple bond results in much augmentation of the bioactivities
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