Characterization of a yellow compound isolated from the marine sponge Phakellia flabellata

Sharma, Gurdial M.; Buyer, Jeffrey S.; Pomerantz, Mark W.

doi:10.1039/c39800000435

Cited by 70 publications

(48 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The active compound was identified as DBH ( Fig. 1) by analysis of its mass spectrometry and NMR data and comparison with published values (57). DBH was identified first in 1980 as a yellow compound from the sponge Phakellia flabelata (57).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of the G2 DNA Damage Checkpoint and of Protein Kinases Chk1 and Chk2 by the Marine Sponge Alkaloid Debromohymenialdisine

Curman

Cinel

Williams

et al. 2001

Journal of Biological Chemistry

121

View full text Add to dashboard Cite

Cells can respond to DNA damage by activating checkpoints that delay cell cycle progression and allow time for DNA repair. Chemical inhibitors of the G 2 phase DNA damage checkpoint may be used as tools to understand better how the checkpoint is regulated and may be used to sensitize cancer cells to DNA-damaging therapies. However, few inhibitors are known. We used a cell-based assay to screen natural extracts for G 2 checkpoint inhibitors and identified debromohymenialdisine (DBH) from a marine sponge. DBH is distinct structurally from previously known G 2 checkpoint inhibitors. It inhibited the G 2 checkpoint with an IC 50 of 8 M and showed moderate cytotoxicity (IC 50 ‫؍‬ 25 M) toward MCF-7 cells. DBH inhibited the checkpoint kinases Chk1 (IC 50 ‫؍‬ 3 M) and Chk2 (IC 50 ‫؍‬ 3.5 M) but not ataxiatelangiectasia mutated (ATM), ATM-Rad3-related protein, or DNA-dependent protein kinase in vitro, indicating that it blocks two major branches of the checkpoint pathway downstream of ATM. It did not cause the activation or inhibition of different signal transduction proteins, as determined by mobility shift analysis in Western blots, suggesting that it inhibits a narrow range of protein kinases in vivo.

show abstract

Section: Resultsmentioning

confidence: 99%

“…1) by analysis of its mass spectrometry and NMR data and comparison with published values (57). DBH was identified first in 1980 as a yellow compound from the sponge Phakellia flabelata (57). The extract also contained minor amounts of the structurally related compounds hymenialdisine, debromoaxinohydantoin, and debromopyrrololactam (Fig.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the G2 DNA Damage Checkpoint and of Protein Kinases Chk1 and Chk2 by the Marine Sponge Alkaloid Debromohymenialdisine

Curman

Cinel

Williams

et al. 2001

Journal of Biological Chemistry

121

View full text Add to dashboard Cite

show abstract

“…Although previously isolated over twenty years before from the sponge Phakellia flabelata, DBH is structurally dissimilar to any previously isolated G 2 checkpoint inhibitor, Fig. (6) [136]. Hymenialdisine and DBH inhibited G 2 checkpoint-mediated transition into mitosis (IC 50 s = 6 ± 3 μM and 8 ± 4 μM, respectively).…”

Section: Checkpoint Kinases and Dual Specificity Phosphatasesmentioning

confidence: 99%

Mechanism Targeted Discovery of Antitumor Marine Natural Products

Nagle¹,

Zhou²,

Mora³

et al. 2004

Current Medicinal Chemistry

View full text Add to dashboard Cite

Antitumor drug discovery programs aim to identify chemical entities for use in the treatment of cancer. Many strategies have been used to achieve this objective. Natural products have always played a major role in anticancer medicine and the unique metabolites produced by marine organisms have increasingly become major players in antitumor drug discovery. Rapid advances have occurred in the understanding of tumor biology and molecular medicine. New insights into mechanisms responsible for neoplastic disease are significantly changing the general philosophical approach towards cancer treatment. Recently identified molecular targets have created exciting new means for disrupting tumor-specific cell signaling, cell division, energy metabolism, gene expression, drug resistance, and blood supply. Such tumor-specific treatments could someday decrease our reliance on traditional cytotoxicity-based chemotherapy and provide new less toxic treatment options with significantly fewer side effects. Novel molecular targets and state-of-the-art molecular mechanism-based screening methods have revitalized antitumor research and these changes are becoming an ever-increasing component of modern antitumor marine natural products research. This review describes marine natural products identified using tumor-specific mechanism-based assays for regulators of angiogenesis, apoptosis, cell cycle, macromolecule synthesis, mitochondrial respiration, mitosis, multidrug efflux, and signal transduction. Special emphasis is placed on natural products directly discovered using molecular mechanism-based screening.

show abstract

“…124 In addition, the 10E-geometrical isomers were reported as minor constituents of the sponge in 1996. 125 Debromohymenialdisine (DBH) has been identified as a potent anti-inflammatory agent, which led to its being patented for the treatment of rheumatoid arthritis by SmithKline Beecham (SKB, now Glaxo SmithKline) and for osteoarthritis (by OsteoArthritis Sciences Inc., now defunct) and as a protein kinase C inhibitor by SKB.…”

Section: Stylotella Aurantiummentioning

confidence: 99%