New aplysiatoxin derivatives from the Okinawan cyanobacterium Moorea producens

Nagai, Hiroshi; Watanabe, Megumi; Sato, Shingo; Kawaguchi, Mioko; Xiao, Yue-Yun; Hayashi, Kazutaka; Watanabe, Ryuichi; Uchida, Hajime; Satake, Masayuki

doi:10.1016/j.tet.2019.03.020

Cited by 27 publications

(42 citation statements)

References 29 publications

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“…The methoxy (Me-32) proton at δ H 3.22 was confirmed to be bonded to C-15 via the HMBC spectrum. The existence of a γ-lactone was deduced from the unsaturation number and the proton chemical shift of H-30 at δ H 4.84, which was close to that of the corresponding peak in 17-bromo-30-methyloscillatoxin D (δ H 4.81) [10]. The HMBC correlation between H-29 at δ H 5.54 and C-1 (δ C 166.6) confirmed the existence of an ester linkage between C-1 and C-29.…”

Section: Resultsmentioning

confidence: 89%

“…The HSQC spectra (Figure S3) of compound 1 showed seven methyls (two singlets, four doublets, and a methoxy), four methylenes, three methines bonded to methyls in the aliphatic region, four oxygenated methines, two olefinic methines, and three aromatic protons in the bromophenol side chain and nine quaternary (one aliphatic, two olefinic, three aromatic in the bromophenol, two esters, and one ketone) carbons (Table 1). The carbon signal at δ C 197.4 and an HMBC (Figure S4) correlation from Me-26 (δ H 1.08) to the ketone suggested that compound 1 was related to 17-bromo-30-methyloscillatoxin D ( 2 ) [10,23]. Analogously to 17-bromo-30-methyloscillatoxin D ( 2 ), connectivity was observed between the H-4 (Me-26) and H 2 -5 protons in the 1 H– 1 H COSY spectrum (Figure 2, Figure S5), although the methine singlet of H-2 in 17-bromo-30-methyloscillatoxin D was not observed.…”

Section: Resultsmentioning

confidence: 99%

“…A partial structure from H-8 to H-12 was assigned by analysis the 1 H– 1 H COSY spectrum. The proton chemical shifts of H-8 and H-9 suggested that these peaks corresponded to olefinic protons; these peaks were shifted downfield from δ H 5.78 and δ H 5.52 in 17-bromo-30-methyloscillatoxin D ( 2 ) [10] to δ H 6.19 and δ H 6.07 in compound 1 , respectively. In addition to this, HMBC correlations between H-8 and C-2/C-7 were observed.…”

Section: Resultsmentioning

confidence: 99%

“…A cyanobacterial sample collected at this site during the 2010 mass occurrence was used in this study. In a recent study, we identified 15 aplysiatoxin derivatives in this Okinawan cyanobacteria sample [10]. Aplysiatoxins have been shown to act as protein kinase C (PKC) activators and potent tumor promoting compounds [11,12,13,14,15]; their toxicity results from their high PKC activation potency [11,12,13,14,15].…”

Section: Introductionmentioning

confidence: 99%

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Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium

Nagai

Sato

Iida

et al. 2019

Toxins

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Cyanobacteria have been shown to produce a number of bioactive compounds, including toxins. Some bioactive compounds obtained from a marine cyanobacterium Moorea producens (formerly Lyngbya majuscula) have been recognized as drug leads; one of these compounds is aplysiatoxin. We have isolated various aplysiatoxin derivatives from a M. producens sample obtained from the Okinawan coastal area. The frozen sample was extracted with organic solvents. The ethyl acetate layer was obtained from the crude extracts via liquid–liquid partitioning, then separated by HPLC using a reversed-phase column. Finally, 1.1 mg of the compound was isolated. The chemical structure of the isolated compound was elucidated with spectroscopic methods, using HR-MS and 1D and 2D NMR techniques, and was revealed to be oscillatoxin I, a new member of the aplysiatoxin family. Oscillatoxin I showed cytotoxicity against the L1210 mouse lymphoma cell line and diatom growth-inhibition activity against the marine diatom Nitzschia amabilis.

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium

Nagai

Sato

Iida

et al. 2019

Toxins

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“…For all of the aplysiatoxin derivatives previously reported, the absolute configurations of C9-C12 are R, S, R, R. However, in this article, the altered absolute configurations at C9-C12 (S, R, S, S) of compound 1 is first reported. Through structural analysis, a plausible biosynthetic pathway is postulated in Figure S19 [33]. We speculated that the different absolute configurations of C9-C12 was Mar.…”

Section: Structure Elucidation Of the New Compoundsmentioning

confidence: 99%

Two New Neo-debromoaplysiatoxins—A Pair of Stereoisomers Exhibiting Potent Kv1.5 Ion Channel Inhibition Activities

et al. 2019

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A pair of stereoisomers possessing novel structures with 6/6/5 fused-ring systems, neo-debromoaplysiatoxin E (1) and neo-debromoaplysiatoxin F (2), were isolated from the marine cyanobacterium Lyngbya sp. Their structures were elucidated using various spectroscopic techniques including high resolution electrospray ionization mass spectroscopy (HRESIMS) and nuclear magnetic resonance (NMR). The absolute stereochemistry was determined by calculated electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR shift calculation followed by DP4+ analysis. Significantly, this is the first report on aplysiatoxin derivatives with different absolute configurations at C9-C12 (1: 9S, 10R, 11S, 12S; 2: 9R, 10S, 11R, 12R). Compounds 1 and 2 exhibited potent blocking activities against Kv1.5 with IC 50 values of 1.22 ± 0.22 µM and 2.85 ± 0.29 µM, respectively.

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Chemistry, Biosynthesis, and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

et al. 2022

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Comprehensive Summary Natural products derived from marine microorganisms have been received great attention as a potential source of new compound entities for drug discovery. The unique marine environment brings us a large group of halogen‐containing natural products with abundant biological functionality and good drugability. Meanwhile, biosynthetically halogenated reactions are known as a significant strategy used to increase the pharmacological activities and pharmacokinetic properties of compounds. Given that a tremendous increase in the number of new halogenated compounds from marine microorganisms in the last five years, it is necessary to summarize these compounds with their diverse structures and promising bioactivities. In this review, we have summarized the chemistry, biosynthesis (related halogenases), and biological activity of a total of 316 naturally halogenated compounds from marine microorganisms covering the period of 2015 to May 2021. Those reviewed chlorinated and brominated compounds with the ratio of 9 : 1 were predominantly originated from 36 genera of fungi (62%) and 9 bacterial strains (38%) with cytotoxic, antibacterial, and enzyme inhibitory activities, structural types of which are polyketides (38%), alkaloids (27%), phenols (11%), and others. This review would provide a plenty variety of promising lead halogenated compounds for drug discovery and inspire the development of new pharmaceutical agents.

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New aplysiatoxin derivatives from the Okinawan cyanobacterium Moorea producens

Cited by 27 publications

References 29 publications

Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium

Oscillatoxin I: A New Aplysiatoxin Derivative, from a Marine Cyanobacterium

Two New Neo-debromoaplysiatoxins—A Pair of Stereoisomers Exhibiting Potent Kv1.5 Ion Channel Inhibition Activities

Chemistry, Biosynthesis, and Biological Activity of Halogenated Compounds Produced by Marine Microorganisms

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