Nostodione A, a Novel Mitotic Spindle Poison from a Blue-Green Alga Nostoc commune

Kobayashi, Akio; Kajiyama, Shin’ichiro; Inawaka, Kunifumi; Kanzaki, Hiroshi; Kawazu, Kazuyoshi

doi:10.1515/znc-1994-7-812

Cited by 40 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, microalgae have yielded a number of potentially useful antiproliferative agents, such as curacin D, the cryptophycin family of compounds, and nostodione A (Kobayashi et al, 1994;Marquez et al, 1998;Wagner et al, 1999). Another compound, closely related to nostodione A, is scytonemin ( Fig.…”

mentioning

confidence: 99%

The Identification and Characterization of the Marine Natural Product Scytonemin as a Novel Antiproliferative Pharmacophore

Stevenson¹,

Capper²,

Roshak³

et al. 2002

J Pharmacol Exp Ther

188

110

View full text Add to dashboard Cite

Marine natural products provide a rich source of chemical diversity that can be used to design and develop new, potentially useful therapeutic agents. We report here that scytonemin, a pigment isolated from cyanobacteria, is the first described small molecule inhibitor of human polo-like kinase, a serine/threonine kinase that plays an integral role in regulating the G 2 /M transition in the cell cycle. Scytonemin inhibited polo-like kinase 1 activity in a concentration-dependent manner with an IC 50 of 2 M against the recombinant enzyme. Biochemical analysis showed that scytonemin reduced GST-polo-like kinase 1 activity in a time-independent fashion, suggesting reversibility, and with a mixed-competition mechanism with respect to ATP. Although scytonemin was less potent against protein kinase A and Tie2, a tyrosine kinase, it did inhibit other cell cycle-regulatory kinases like Myt1, checkpoint kinase 1, cyclin-dependent kinase 1/cyclin B, and protein kinase C␤2 with IC 50 values similar to that seen for polo-like kinase 1. Consistent with these effects, scytonemin effectively attenuated, without chemical toxicity, the growth factor-or mitogen-induced proliferation of three cell types commonly implicated in inflammatory hyperproliferation. Similarly, scytonemin (up to 10 M) was not cytotoxic to nonproliferating endotoxin-stimulated human monocytes. In addition, Jurkat T cells treated with scytonemin were induced to undergo apoptosis in a non-cell cycle-dependent manner consistent with its activities on multiple kinases. Here we propose that scytonemin's dimeric structure, unique among natural products, may be a valuable template for the development of more potent and selective kinase inhibitors used for the treatment of hyperproliferative disorders.

show abstract

mentioning

confidence: 99%

The Identification and Characterization of the Marine Natural Product Scytonemin as a Novel Antiproliferative Pharmacophore

Stevenson¹,

Capper²,

Roshak³

et al. 2002

J Pharmacol Exp Ther

188

110

View full text Add to dashboard Cite

show abstract

“…Later, a postulated intermediate, nostodione was isolated from a Nostoc species. [154] Nostodione, which was also obtained in a different study by ozonolysis of scytonemin, [153] could be reductively dimerized to the dimeric parent structure, scytonemin. Another indole, prenostodione, was isolated and postulated to serve as precursor to nostodione.…”

Section: In the Context Of A Screening Program Of Cyanobacterial Metamentioning

confidence: 92%

“…Nostoc commune (nostodione [154] ) and Nostoc sp (prenostodione [155] ). The carbolinium alkaloid nostocarboline was isolated from the freshwater cyanobacterium Nostoc 78-12A, its structure characterized and synthesized Fig.…”

Section: In the Context Of A Screening Program Of Cyanobacterial Metamentioning

confidence: 99%

Secondary Metabolites from Cyanobacteria: Complex Structures and Powerful Bioactivities

Gademann¹,

Portmann

2008

COC

229

168

View full text Add to dashboard Cite

This review presents natural products from cyanobacteria. Several classes of secondary metabolites are highlighted. Toxic metabolites from these prokaryotic photosynthetic organisms include compounds such as microcystin, anatoxin and saxitoxin, which display hepatotoxicity and neurotoxicity. Their potential as drugs in cancer therapy is discussed based on the cryptophycin class of potent cytotoxic agents. The next part of this review highlights iron chelators from cyanobacteria, including schizokinen, synechobactin and anachelin. The biogenesis of anachelin is investigated as its mechanism of iron acquisition. Several indole alkaloids are then reviewed, from simple carbolines such as bauerines and nostocarboline to complex polycyclic structures such as hapalindole, welwitindolinone and ambiguine. The latter compounds present fascinating structure combined with powerful bioactivities and interesting biogenetic pathways. In the last part, protease inhibitors from cyanobacteria are discussed (cyanopeptolins, micropeptin and oscillapeptin) and their structure/activity relationships and selectivity for trypsin / chymotrypsin are presented. All these examples highlight the large structural variety of cyanobacterial metabolites combined with powerful biological activities. Cyanobacteria can thus be considered a prime source both for novel bioactive compounds and for leads for drugs.

show abstract

“…For examples of -diketone oxidations using selenium dioxide, see: Gribble et al (1988); Xu et al (2002); Belsey et al (2006). For related cyclopenta [b]indolone alkaloids and their analogues, see: Cheng et al (1991); Garcia-Pichel & Castenholz (1991); Garcia-Pichel et al (1992); Proteau et al (1993); Ekebergh et al (2011); Kobayashi et al (1994); Jacquemard et al (2004); Ploutno & Carmeli (2001). For standard bond lengths, see: Allen et al (1987).…”

Section: Related Literaturementioning

confidence: 99%

3,3-Dimethyl-1,2,3,4-tetrahydrocyclopenta[b]indole-1,2-dione (bruceolline E)

et al. 2012

View full text Add to dashboard Cite

show abstract

Nostodione A, a Novel Mitotic Spindle Poison from a Blue-Green Alga Nostoc commune

Cited by 40 publications

References 0 publications

The Identification and Characterization of the Marine Natural Product Scytonemin as a Novel Antiproliferative Pharmacophore

The Identification and Characterization of the Marine Natural Product Scytonemin as a Novel Antiproliferative Pharmacophore

Secondary Metabolites from Cyanobacteria: Complex Structures and Powerful Bioactivities

3,3-Dimethyl-1,2,3,4-tetrahydrocyclopenta[b]indole-1,2-dione (bruceolline E)

Contact Info

Product

Resources

About