Bioactive marine metabolites. 25. Further kabiramides and halichondramides, cytotoxic macrolides embracing trisoxazole, from the Hexabranchus egg masses

Matsunaga, Shigeki; Fusetani, Nobuhiro; Hashimoto, Kanehisa; Koseki, Koshi; Noma, Masana; Noguchi, Hiroshi; Sankawa, Ushio

doi:10.1021/jo00267a024

Cited by 96 publications

(61 citation statements)

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“…Numerous bis-and tris-oxazoles, as well as a few oxazole-thiazoles, have been isolated from marine organisms, whereas linked thiazole-containing natural products have generally been obtained from microorganisms. 1 Marine organism secondary metabolites such as ulapualides, 2 halichondramides, 3 kabiramides, 3 mycalolides, 4 halishigamides, 5 and jaspisamides, 6 all contain a trisoxazole fragment. These compounds show a broad range of unusual biological activities.…”

Section: Introductionmentioning

confidence: 99%

Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

et al. 2007

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Section: Introductionmentioning

confidence: 99%

Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

et al. 2007

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“…All of these compounds, which include the aplyronins, mycalolides (9, 10) ulapualides (11), halichondramides (12,13), and kabiramides (12,14) (Fig. 1B) share the characteristic of a macrocyclic ring and tail, where the primary region of variability within and between different families of macrolides is associated with the macrocyclic component.…”

mentioning

confidence: 99%

Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity

Allingham

Zampella

D’Auria

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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Marine macrolides that disrupt the actin cytoskeleton are promising candidates for cancer treatment. Here, we present the actinbound x-ray crystal structures of reidispongiolide A and C and sphinxolide B, three marine macrolides found among a recently discovered family of cytotoxic compounds. Their structures allow unequivocal assignment of the absolute configuration for each compound. A comparison of their actin-binding site to macrolides found in the trisoxazole family, as well as the divalent macrolide, swinholide A, reveals the existence of a common binding surface for a defined segment of their macrocyclic ring. This surface is located on a hydrophobic patch adjacent to the cleft separating domains 1 and 3 at the barbed-end of actin. The large area surrounding this surface accommodates a wide variety of conformations and designs observed in the macrocyclic component of barbed-end-targeting macrolides. Conversely, the binding pocket for the macrolide tail, located within the cleft itself, shows very limited variation. Functional characterization of these macrolides by using in vitro actin filament severing and polymerization assays demonstrate the necessity of the N-methyl-vinylformamide moiety at the terminus of the macrolide tail for toxin potency. These analyses also show the importance of stable interactions between the macrocyclic ring and the hydrophobic patch on actin for modifying filament structure and how this stability can be compromised by subtle changes in macrolactone ring composition. By identifying the essential components of these complex natural products that underlie their high actin affinity, we have established a framework for designing new therapeutic agents.cytoskeleton ͉ cytotoxins ͉ macrolides ͉ marine natural products

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“…The nitrile 43 was an active inhibitor of the proliferation of the parasite Leishmania mexicana with an LD 50 value of 12 µg/mL [25]. A library of 22 pyrrole-2-carboxaldehydes including the mycalazals 3-13 (49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59), the mycalenitriles 1-3 (60)(61)(62), and the known pyrrole-2-carboxaldehydes 16,18,35,36,41,43,63, and 64 were screened against a panel of cell lines (LN-caP, IGROV, SK-BR3, SK-MEL-28, A-549, K-562, PANCI, LOVO, and HeLa cell lines), which resulted in some interesting structure activity observations (see [27] for specific GI 50 values). The authors compared the LN-caP cell line inhibition with the structures of the compounds and found that activity was associated with the presence of a single double bond, activity decreased with three double bonds, and was lost completely with two double bonds or saturated alkyl chains [27].…”

Section: Pyrrole Derivativesmentioning

confidence: 99%

“…Additionally, trisoxazole macrolides have also been reported from other non-sponge sources such as the egg masses of the nudibranch Hexabranchus sp. [58,[61][62][63]. Trisoxazole macrolides have displayed a range of biological activities, including cytotoxic, proteasome inhibiting, actin-depolymerising, antimalarial, and antifungal activities.…”

Section: Polyketides Macrolidesmentioning

confidence: 99%

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

2016

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Sponges are a useful source of bioactive natural products. Members of the family Mycalidae, in particular, have provided a variety of chemical structures including alkaloids, polyketides, terpene endoperoxides, peptides, and lipids. This review highlights the compounds isolated from Mycalid sponges and their associated biological activities. A diverse group of 190 compounds have been reported from over 40 specimens contained in 49 references. Over half of the studies have reported on the biological activities for the compounds isolated. The polyketides, in particular the macrolides, displayed potent cytotoxic activities (

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Bioactive marine metabolites. 25. Further kabiramides and halichondramides, cytotoxic macrolides embracing trisoxazole, from the Hexabranchus egg masses

Cited by 96 publications

References 0 publications

Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

Preparation of penta-azole containing cyclopeptides: challenges in macrocyclization

Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

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