Eudistomins A-Q, .beta.-carbolines from the antiviral Caribbean tunicate Eudistoma olivaceum

Rinehart, Kenneth L.; Kobayashi, Jun’ichi; Harbour, Gary C.; Gilmore, Jeremy; Mascal, Mark; Holt, Tom G.; Shield, Lois S.; Lafargue, F.

doi:10.1021/ja00245a031

Cited by 246 publications

(107 citation statements)

References 5 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…24,25) Iejimalide A is also expected to be a promising lead compound for a novel type of antiosteoporosis agent, since V-ATPase inhibitors trigger apoptotic cell death of osteoclasts. 24,25) Eudistomin C, a β-carboline alkaloid isolated from a Caribbean compound tunicate Eudistoma olivaseum, displayed extremely potent antiviral activity against DNA and RNA viruses 26,27) (Fig. 9).…”

Section: Bioactive Natural Products From Marine Compound Tunicatesmentioning

confidence: 99%

Search for New Bioactive Marine Natural Products and Application to Drug Development

Kobayashi

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Natural products are well recognized as an important source of lead compounds in drug development. During the past >30 years, we have discovered >1000 novel bioactive natural products from Okinawan marine organisms (sponges, tunicates, cone shells, etc.) and microorganisms (fungi, bacteria, dinoflagellates, etc.). Some of them are used as bioprobes useful for basic studies of life sciences, while others are expected to be candidates of drug leads.

show abstract

Section: Bioactive Natural Products From Marine Compound Tunicatesmentioning

confidence: 99%

Search for New Bioactive Marine Natural Products and Application to Drug Development

Kobayashi

2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…This indicates that more than one compound in combination is probably responsible for the algicidal activity and that the effect is likely to be synergistic rather than simply additive. Probable synergistic effects of multiple antifouling compounds have been reported with extract fractions of sea stars (Greer et al 2006 ) and individual alkaloids elaborated by a tunicate have been reported to have synergistic effects in controlling biomedically relevant bacteria (Rinehart et al 1987 ). Otherwise, we are not aware of documented examples of synergistic effects of bioactive compounds from marine organisms.…”

mentioning

confidence: 95%

Algicidal activity and potential antifouling defenses in macroalgae from the western Antarctic Peninsula including probable synergistic effects of multiple compounds

et al. 2012

View full text Add to dashboard Cite

Insoluble crude extract fractions of 11 species of Antarctic macroalgae were screened for algicidal activity against sympatric diatoms. Medium pressure liquid chromatography (MPLC) fractions of soluble extracts of four species were also screened. Levels of activity in insoluble fractions were lower than in previously examined corresponding soluble fractions. Combined MPLC fractions had lower activity than unfractionated extracts in three species, but in two, specifi c fractions with activity were identifi ed. Combined soluble fractions of a fourth species retained strong activity but no individual fraction had activity even at tenfold higher concentrations, indicating that activity probably results from synergistic interactions between multiple compounds.

show abstract

“…For example, comparison of the biological data of compounds 6 and 19, as well as compounds 16 and 29, revealed that B compounds (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) are not always superior to A compounds (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Both compounds 29 and 19, which contain a 3,4-dihydro-b-carboline skeleton showed notable difference in activity.…”

Section: Resultsmentioning

confidence: 99%

“…[4][5][6] Particularly interesting targets include such compounds as eudistomins 7,8) and manzamines, 9,10) which were isolated from marine tunicates and sponges, respectively. As a class, the oxathiazepine containing eudistomines exhibited potent inhibitory activity toward DNA virus HSV-1.…”

mentioning

confidence: 99%

The Preparation and Evaluation of 1-Substituted 1,2,3,4-Tetrahydro- and 3,4-Dihydro-.BETA.-carboline Derivatives as Potential Antitumor Agents

et al. 2005

View full text Add to dashboard Cite

Marine natural products which contain a b-carboline skeleton are widely distributed in marine invertebrates. 1-3)The discovery of natural b-carboline metabolites as potent antitumor and antiviral agents has stimulated great interest in the synthetic and pharmacological studies of b-carboline derivatives. [4][5][6] Particularly interesting targets include such compounds as eudistomins 7,8) and manzamines, 9,10) which were isolated from marine tunicates and sponges, respectively. As a class, the oxathiazepine containing eudistomines exhibited potent inhibitory activity toward DNA virus HSV-1. In addition, the antiviral eudistomines C (1) and E (2) were also found active against HSV-2, the Vaccinia virus and RNA viruses.11) The novel structures of manzamines, however, were reported to possess potent antitumor, 12,13) antibacterial, antifungal, and anti-HIV activities.14) The most active was manzamine A (3), a principal metabolite from several species of sponges, which showed cytotoxicity against murine P-388 cells at 0.07 mg/ml. 15) Our previous report has revealed that manzamine A-D and H exhibited potent cytotoxicities against human KB-16, A-549 and HT-29 tumor cell lines. 16)The common b-carboline or 1,2,3,4-tetrahydro-b-carboline moieties appear to be important for the biological activity. In order to investigate the essential structural features for the antitumor activity of manzamine A (3), the synthesis of 1-substituted 1,2,3,4-tetrahydro-and 3,4-dihydro-b-carboline derivatives were initiated. The difficult isolation of manzamine A (3) from sponge and its limited source make this current program more important and significant. A facile synthetic method by the application of Pictet-Spengler reaction [17][18][19][20] and DDQ oxidation 21) allowed the preparation of compounds 4-29. Herein, we wish to report the preparation, characterization and biological evaluation of 1-substituted 1,2,3,4-tetrahydro-and 3,4-dihydro-b-carboline derivatives. Results and DiscussionAs summarized in Chart 1, compounds 4-16 were synthesized from tryptamine (I) and substituted benzaldehydes via Pictet-Spengler cyclization. Subsequent oxidation of 1,2,3,4-tetrahydro-b-carbolines (4-16, A compounds) by DDQ furnished 3,4-dihydro-b-carboline derivatives (17-29, B compounds). The spectral data for 4-29 are illustrated in Experimental. Table 1 shows the biological results for compounds 4-29 and manzamine A (3) as tested against murine P-388 (leukemia) and human tumor cell lines, including KB-16 (nasopharyngeal carcinoma), A-549 (lung adenocarcinoma) and HT-29 (colon adenocarcinoma) in vitro. All of the compounds exhibited promising activity except for 19, which had no activity toward the four tumor cell lines. Among them, compound 29 exhibited the most potent activity against all tested tumor cells. For P-388 inhibitory activity, compounds 8 and 29 were more potent than or comparable to 3. Compounds 4, 12, 14, 15, 25 and 28 showed potent to moderate activity. As for KB-16 cell cytotoxicity, compound 29 was equal in potency to manzamine A ...

show abstract

Eudistomins A-Q, .beta.-carbolines from the antiviral Caribbean tunicate Eudistoma olivaceum

Cited by 246 publications

References 5 publications

Search for New Bioactive Marine Natural Products and Application to Drug Development

Search for New Bioactive Marine Natural Products and Application to Drug Development

Algicidal activity and potential antifouling defenses in macroalgae from the western Antarctic Peninsula including probable synergistic effects of multiple compounds

The Preparation and Evaluation of 1-Substituted 1,2,3,4-Tetrahydro- and 3,4-Dihydro-.BETA.-carboline Derivatives as Potential Antitumor Agents

Contact Info

Product

Resources

About