Amphidinolides G and H: new potent cytotoxic macrolides from the cultured symbiotic dinoflagellate Amphidinium sp

Kobayashi, Jun’ichi; Shigemori, Hideyuki; Ishibashi, Masami; Yamasu, Terufumi; Harada, Hiroshi; Sasaki, Takuma

doi:10.1021/jo00017a044

Cited by 84 publications

(63 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest that amphidinolide B (2) enhances an interaction of actin and myosin directly and increases Ca 2ϩ sensitivity of the contractile apparatus mediated through troponin-tropomyosin system, resulting in an increase in the ATPase activity of actomyosin and thus enhances the contractile response of myofilament [44]. The molecular target of amphidinolide H (8) [25,26] has been investigated as follows [45,46]. The analysis of phenotypes of amphidinolide H-treated cells suggested that amphidinolide H (8) disrupt the actin organization in the cells, and the polymerization/depolymerization assay using purified actin indicated that amphidinolide H (8) stimulated actin polymerization and stabilized F-actin.…”

Section: Mechanism Of Action Of Amphidinolides B and Hmentioning

confidence: 96%

“…Amphidhinolide H (8) is a 26-membered macrolide possessing an epoxide, six C 1 branches, and four hydroxyl groups with potent cytotoxicity against L1210 and KB cells (IC 50 : 0.00048 and 0.00052 m g/ml, respectively) [25,26]. The relative configurations at nine chiral centers in 8 were deduced from a single crystal X-ray diffraction analysis.…”

Section: -2 Amphidinolide Hmentioning

confidence: 99%

“…Thirty-four cytotoxic macrolides, designated amphidinolides AϳH (1ϳ8), JϳS (9ϳ18), T1 (19), UϳY (20ϳ24), G2 (25), G3 (26), H2ϳH5 (27ϳ30), and T2ϳT5 (31ϳ34), have been isolated from Amphidinium sp. by our group untill 2003, ( Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

Kobayashi

2008

J Antibiot

144

View full text Add to dashboard Cite

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...

show abstract

Section: Mechanism Of Action Of Amphidinolides B and Hmentioning

confidence: 96%

Section: -2 Amphidinolide Hmentioning

confidence: 99%

See 1 more Smart Citation

Amphidinolides and Its Related Macrolides from Marine Dinoflagellates

Kobayashi

2008

J Antibiot

144

View full text Add to dashboard Cite

show abstract

“…3 The ring sizes of the macrolactones range from 12 to 29 and all of them show significant biological activity. amphidinolide H2 (2) R 2 = CH 3 , R 4 , R 6 = OH, R 1 , R 3 , R 5 = H, Δ 6,7 amphidinolide H3 (3) R 1 = CH 3 , R 3 , R 5 = OH, R 2 , R 4 , R 6 = H, Δ 6,7 amphidinolide H4 (4) R 1 = CH 3 , R 3 , R 6 = OH, R 2 , R 4 , R 5 = H, 6,7-dihydro amphidinolide H5 (5) R 2 = CH 3 , R 4 , R 6 = OH, R 1 , R 3 , R 5 = H, 6,7-dihydro amphidinolide H (1) Figure 1 The amphidinolides of the H-group.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the Northern Hemisphere of Amphidinolide H2

Liesener¹,

Jannsen²,

Kalesse³

2006

Synthesis

View full text Add to dashboard Cite

The stereoselective synthesis of the fully functionalized northern hemisphere of the marine natural product amphidinolide H2 is described. A vinylogous Mukaiyama aldol reaction and enzymatic desymmetrization of a meso compound are the key steps in the fragment synthesis. A stereoselective acetate aldol coupling and a 1,3-anti-reduction of the resulting b-hydroxy ketone complete the synthesis of the C14-C26 fragment.

show abstract

“…From the dinoflagellate Amphidinium (strain Y-42), amphidinolide W (1) in addition to amphidinolide G and H 9,10) (2) and their related macrolides were isolated previously.…”

mentioning

confidence: 99%