Structures of new amphidinols with truncated polyhydroxyl chain and their membrane-permeabilizing activities

Morsy, Nagy; Houdai, Toshihiro; Matsuoka, Shigeru; Matsumori, Nobuaki; Adachi, Seiji; Oishi, Tohru; Murata, Michio; Iwashita, Takashi; Fujita, Tsuyoshi

doi:10.1016/j.bmc.2006.06.012

Cited by 79 publications

(54 citation statements)

References 22 publications

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“…This formation is also seen in previous studies on 4 . [13a] While it is understood that the limitations of solubility of KmTx’s and sterols limits the ability of the NMR binding experiment to closely mimic the aqueous external membrane environment, the results from this study corroborate what has previously been seen for 4 . These interactions would aid the pore formation of KmTx in the sterol-containing cellular membrane.…”

supporting

confidence: 82%

“…[12] Whether this pore follows the hypothesized barrel-stave model as predicted for amphotericin B or a toroidal pore model as predicted for 4 is still under investigation. [13] The configuration of the sterol 3-OH group has also been shown to be important for activity in this class of molecules. For 4 , pore formation was only seen when 3β-OH sterols were present in the membrane and not in the presence of 3α-OH sterols such as epicholesterol.…”

mentioning

confidence: 99%

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Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action

Waters

Place

et al. 2015

Angew Chem Int Ed

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Following the publication of karlotoxin 2 (KmTx2, 1), the harmful algal bloom dinoflagellate Karlodinium sp. was collected from oceans and bays throughout the world and scrutinized to identify additional biologically active complex polyketides. The structure of 1 was validated and revised at C49 using computational NMR tools including J-based configurational analysis (JBCA) and chemical shift (CS) calculations. The characterization of 2 new compounds [KmTx8 and 9 (2–3)] was achieved through overlaid 2D HSQC NMR techniques, while the relative configurations were determined by comparison to 1 and computational chemical shift calculations. The detailed evaluation of 2 using the NCI-60 cell lines, NMR binding studies and an assessment of the literature supports an MoA of targeting cancer-cell membranes especially of cytostatic tumors. This is uniquely different from the MoA of current agents employed in the control of cancers such as leukemia and lung cancer for which 2 shows sensitivity.

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confidence: 82%

mentioning

confidence: 99%

Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action

Waters

Place

et al. 2015

Angew Chem Int Ed

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“…Measurements of lysis of human erythrocytes in the presence of varying concentrations of purified 1 showed an EC50 of 63 nM. This high level of potency is comparable to that of 3 , the most hemolytic amphidinol, which has been reported in different studies with human erythrocytes to have EC50 values of 9 nM,23 150 nM,12 250 nM,37 and 400 nM 38. The discovery of KmTx 1 adds to the growing list of amphipathic toxins produced by dinoflagellates, suggesting that the production of these compounds is an effective strategy adopted by these organisms to avoid predation and, in the case of K. veneficum , for prey capture 17…”

supporting

confidence: 62%

Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum

Wagoner

Deeds

Satake

et al. 2008

Tetrahedron Letters

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The karlotoxins (KmTxs) are a family of compounds produced by the dinoflagellate Karlodinium veneficum that cause membrane permeabilization. The structure of KmTx 1, determined using extensive 2D NMR spectroscopy, is very similar to the amphidinols and related compounds, though KmTx 1 features unique structural modifications of the conserved core region. The structure of KmTx 1 differs from that reported for KmTx 2, the only other reported karlotoxin to date, in lacking chlorination at its terminal alkene and possessing a hydrophobic arm that is two carbons longer.

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“…[11][12][13] In terms of carbon-chain length, however, ZAD-D (1) is an amide consisting of a C 21 acid and a C 27 amine, whereas the amphidinols possess a contiguous carbon chain (C 55 -C 69 ) without nitrogenous functionalities. In addition to the carbon skeleton, the uncommon structural features are the presence of three tetrahydropyran rings and five butadiene chromophores.…”

Section: Resultsmentioning

confidence: 99%

Zooxanthellamide D, a Polyhydroxy Polyene Amide from a Marine Dinoflagellate, and Chemotaxonomic Perspective of the Symbiodinium Polyols

et al. 2007

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A long-chain polyhydroxy polyene amide, zooxanthellamide D (ZAD-D, 1, C54H83NO19), was isolated from a cultured marine dinoflagellate of the genus Symbiodinium. ZAD-D (1) is a polyhydroxy amide consisting of a C22-acid part and a C32-amine part and furnishes three tetrahydropyran rings and six isolated butadiene chromophores. The relative stereochemistry of the tetrahydropyran ring systems was elucidated by NMR techniques. This metabolite showed moderate cytotoxicity against two human tumor cell lines. A phylogenetic tree of Symbiodinium has been updated and compared with the structures of the hitherto isolated polyols of Symbiodinium, zooxanthellatoxins and zooxanthellamides, providing a promising chemotaxonomic perspective for the classification of this morphologically indistinguishable dinoflagellate.

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Structures of new amphidinols with truncated polyhydroxyl chain and their membrane-permeabilizing activities

Cited by 79 publications

References 22 publications

Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action

Stereochemical Studies of the Karlotoxin Class Using NMR Spectroscopy and DP4 Chemical‐Shift Analysis: Insights into their Mechanism of Action

Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum

Zooxanthellamide D, a Polyhydroxy Polyene Amide from a Marine Dinoflagellate, and Chemotaxonomic Perspective of the Symbiodinium Polyols

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