Isolation and Structure of Caribenolide I, a Highly Potent Antitumor Macrolide from a Cultured Free-Swimming Caribbean Dinoflagellate, Amphidinium sp. S1-36-5

Bauer, Ines; Maranda, Lucie; Young, Kurt A.; Shimizu, Yuzuru; Fairchild, Craig R.; Cornell, Laurie; MacBeth, Judy; Huang, Stella

doi:10.1021/jo00109a050

Cited by 72 publications

(51 citation statements)

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“…Although the relative configurations at C-14, C-15, C-16, and C-19 were indicated as shown, the other relative stereochemistry as well as the absolute stereochemistry of 13 have not been determined. Shimizu and co-workers isolated an amphidinolide N-type macrorolide, named caribenolide I [35], from a free-swimming dinoflagellate Amphidinium operculatum ver nov Gibbosum, which showed antitumor activity against murine leukemia P388 in vivo.…”

Section: -4 Amphidinolide Nmentioning

confidence: 99%

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

Kobayashi

2008

J Antibiot

145

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This review covers the recent results described in our publications on several new cytotoxic macrolides isolated from dinoflagellates of the genus Amphidinium in addition to an overview of the isolation, structure elucidation, synthesis, biosynthesis, and bioactivity of a series of cytotoxic macrolides, named amphidinolides, reported so far. IntroductionMarine dinoflagellates, a diverse group of unicellular eukaryotes, have been recognized as real producers of marine toxins responsible to fish and algal poisoning, as well as biologically unique organisms due to their taxonomic position and unusual chromosome structure and composition. Marine dinoflagellates have also proved to be one of the most important source of bioactive natural products, which have been investigated worldwide. We have continuously studied structurally intriguing and biologically interesting bioactive macrolides and polyketides from dinoflagellates Amphidinium sp., which are symbionts of Okinawan marine flatworms Amphiscolops sp.Thirty Culture of Dinoflagellates Amphidinium sp.Large-scale cultures of the dinoflagellates of the genus Amphidinium have been performed using seawater medium enriched with Provasoli's Erd-Schriber (ES) supplement. Static incubation with illumination in a cycle of 16 hours of light and 8 hours of darkness was carried out for two weeks at 25°C. The cultures were harvested by removal of the supernatant through suction and then centrifugation to obtain algal cells. Harvested cells were extracted with MeOH -toluene, and the extracts were subjected to a systematic separation using several chromatographies to yield cytotoxic macrolides [15ϳ26]. Isolation of New Macrolides 3-1. Amphidinolactones A and BA new 13-membered macrolide, amphidinolactone A (38), C 20 H 30 O 4 , was isolated from a strain (Y-25) of a dinoflagellate Amphidinium sp. [15]. Detailed analyses of the 1 H-1 H COSY spectrum of 38 revealed connectivities of a long carbon chain from C-2 to C-20. 1 H and 13 C chemical shifts of CH 2 -2 and CH-12 suggested that C-12 was involved in an ester linkage with C-1. 1 H-1 H couplings of the two disubstituded double bonds at C-5 and C-9 indicated the Z and E geometries, respectively. Geometries of two disubstituted double bonds at C-14 and C-17 were assigned as both Z by NOESY correlations and the carbon chemical shift of C-16, which was a typical value for a methylene carbon between two Z double bonds. Thus, the gross structure of amphidinolactone A was elucidated to be 38. The relative configurations at C-8, C-11, and C-12 in 38 were deduced from NOESY correlations.A new 26-membered macrolide, amphidinolactone B (39), C 32 H 54 O 8 , has been isolated from the same dinoflagellate Amphidinium sp. (strain Y-25) as described above [16]. Detailed analyses of the 1 H-1 H COSY and TOCSY spectra as well as HMBC correlations indicated connectivities of a long carbon chain from C-2 to C-26. 1 H and 13 C chemical shifts of C-25 indicated that C-25 was involved in an ester linkage with C-1. The NOESY correlation for...

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Section: -4 Amphidinolide Nmentioning

confidence: 99%

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

Kobayashi

2008

J Antibiot

145

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“…P388. Of even greater potency was the macrolide caribenolide (8) (Bauer et al, 1996;, which showed a mean IC 50 of 1.6 nM and, likewise, had limited cell line selectivity. Using limited supplies, activity against ip/ip P388 was established (50% lifespan increase), but no distal site antitumor activity could be shown against i.v.…”

Section: Mass Scale Cultivation and Isolation Of Metabolitesmentioning

confidence: 99%

New Anticancer Drugs from Cultured and Collected Marine Organisms

Fenical

Jensen

Kauffman

et al. 2003

Pharmaceutical Biology

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“…In the last decade, some species belonging to this group have gained attention and are being used as a 'model' organism for research into dinoflagellate genetics, polyketide production (including cytotoxins and ichthyotoxins), and photosynthesis (Kobayashi et al 1991;Satake et al 1991;Bauer et al 1994Bauer et al , 1995Paul et al 1996;Houdai et al 2001;Damjanovic et al 2000;Kleima-Foske et al 2000a, b, Ten Lohuis andMiller 1998;Kubota et al 2006). Even though Amphidinium forms a dominant phytobenthos and known to be a nice prey for protistan grazers (Jeong et al 2001), its ecological significance in their role as primary producer, biogeochemical cycling, and food-web dynamics in the benthic system is largely unknown.…”

Section: Identification and Distribution Of Amphidiniummentioning

confidence: 99%

Benthic dinoflagellate blooms in tropical intertidal rock pools: elucidation of photoprotection mechanisms

et al. 2017

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LT-RPs. The observed differences can thus be attributed to the microalgal composition differences and to differences in experienced irradiance of these communities. Dynamic photoinhibition was more prominent in LT-RPs followed by MT-RPs and HT-RPs. The high accumulation of photoprotective pigments in HT-RPs (due to prolong exposure to solar radiation) could be the reason for the differences. The presence of reduced de-epoxidation state and the mid-day depression in F v /F m coupled with elevated σ PSII confirmed dominance of NPQ of reaction centres in HT-RPs compared to other pools. This study concludes that RP planktonic microalgae are eurythermal, euryhaline, and euryphotic. Concerned with increasing harmful algal bloom events further studies on diverse aspects of RP microalgae (including chemical mediated interactions) needs attention.

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Isolation and Structure of Caribenolide I, a Highly Potent Antitumor Macrolide from a Cultured Free-Swimming Caribbean Dinoflagellate, Amphidinium sp. S1-36-5

Cited by 72 publications

References 1 publication

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

New Anticancer Drugs from Cultured and Collected Marine Organisms

Benthic dinoflagellate blooms in tropical intertidal rock pools: elucidation of photoprotection mechanisms

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