Laulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator

Corley, David G.; Herb, Rolf; Moore, Richard E.; Scheuer, Paul J.; Paul, Valerie J.

doi:10.1021/jo00250a053

Cited by 213 publications

(134 citation statements)

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“…Structures of laulimalide site and taxoid site drugs. Position numbers for laulimalide are from Corley et al (1988) and for peloruside A from West et al (2000).…”

Section: Comparison Of Peloruside a With Other Compoundsmentioning

confidence: 99%

Synergistic Effects of Peloruside A and Laulimalide with Taxoid Site Drugs, but Not with Each Other, on Tubulin Assembly

Hamel¹,

Day²,

Miller³

et al. 2006

Mol Pharmacol

124

114

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Previous studies on the drug content of pelleted tubulin polymers suggest that peloruside A binds in the laulimalide site, which is distinct from the taxoid site. In a tubulin assembly system containing microtubule-associated proteins and GTP, however, peloruside A was significantly less active than laulimalide, inducing assembly in a manner that was most similar to sarcodictyins A and B. Because peloruside A thus far seems to be the only compound that mimics the action of laulimalide, we examined combinations of microtubule-stabilizing agents for synergistic effects on tubulin assembly. We found that peloruside A and laulimalide showed no synergism but that both compounds could act synergistically with a number of taxoid site agents [paclitaxel, epothilones A/B, discodermolide, dictyostatin, eleutherobin, the steroid derivative 17␤-acetoxy-2-ethoxy-6-oxo-B-homo-estra-1,3,5(10)-trien-3-ol, and cyclostreptin]. None of the taxoid site compounds showed any synergism with each other. From an initial study with peloruside A and cyclostreptin, we conclude that the synergism phenomenon derives, at least in part, from an apparent lowering of the tubulin critical concentration with drug combinations compared with single drugs. The apparent binding of peloruside A in the laulimalide site led us to attempt construction of a pharmacophore model based on superposition of an energy-minimized structure of peloruside A on the crystal structure of laulimalide. Although the different sizes of the macrocycles limited our ability to superimpose the two molecules, atom correspondences that were observed were consistent with the difficulty so far experienced in creation of fully active analogs of laulimalide.

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“…Structures of laulimalide site and taxoid site drugs. Position numbers for laulimalide are from Corley et al (1988) and for peloruside A from West et al (2000).…”

Section: Comparison Of Peloruside a With Other Compoundsmentioning

confidence: 99%

Synergistic Effects of Peloruside A and Laulimalide with Taxoid Site Drugs, but Not with Each Other, on Tubulin Assembly

Hamel¹,

Day²,

Miller³

et al. 2006

Mol Pharmacol

124

114

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“…1) This nudibranch and other dorid nudibranchs can accumulate secondary metabolites that are derived from dietary organisms in order to protect themselves from predators. [2][3][4] J. funebris is carnivorous and feeds mainly on sponges such as Xestospongia sp., Haliclona sp., Euplacella cf. australis, 5) and Oceanapia sp.…”

mentioning

confidence: 99%

Jorunnamycins A-C, New Stabilized Renieramycin-Type Bistetrahydroisoquinolines Isolated from the Thai Nudibranch Jorunna funebris

Charupant

Suwanborirux

Amnuoypol

et al. 2007

CHEMICAL & PHARMACEUTICAL BULLETIN

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The nudibranch Jorunna funebris (Mollusca: Gastropoda: Opisthobranchia: Nudibranchia: Kentrodorididae) is one of the marine, slug-like invertebrates belonging to phylum Mollusca that lacks a protective hard shell.1) This nudibranch and other dorid nudibranchs can accumulate secondary metabolites that are derived from dietary organisms in order to protect themselves from predators.2-4) J. funebris is carnivorous and feeds mainly on sponges such as Xestospongia sp., Haliclona sp., Euplacella cf. australis, 5) and Oceanapia sp. 6) In 1988, de Silva and Gulavita isolated several simple isoquinolinequinones including renierol acetate (4a), renierol propionate (4b), N-formyl-1,2-dihydrorenierol acetate (5a), and Nformyl-1,2-dihydrorenierol propionate (5b) from Xestospongia sp. and its associated nudibranch J. funebris, but no bistetrahydroisoquinolines.7-9) An in-depth chemical analysis of the mantle and mucus of the Pacific nudibranch J. funebris by Fontana et al. resulted in the isolation of the bistetrahydroisoquinoline jorumycin (6), the primary assay of which revealed cytotoxicity against NIH 3T3 fibroblast cells and against some tumor cell lines, such as P388 mouse lymphoma, A549 human lung carcinoma, HT29 human colon carcinoma, and MEL28 human melanoma, at very low concentrations. 10) Compound 6 shows the promising antitumor properties: however, it is available only in very minute quantities, because 6 has relatively an unstable carbinolamine functional group that may be decomposed during isolation procedure. To obtain sufficient quantities of more stable derivatives with retention of bioactivity, we reported that ecteinascidin 770 was isolated from the Thai tunicate Ecteinascidia thurstoni pretreated with KCN in methanolic buffer solution.11) Furthermore, we have recently succeeded the isolation and structure elucidation of renieramycin M (2m) with gram-scale supply from a Thai sponge Xestospongia sp. that was also pretreated with KCN.12) As series of our search for new metabolites via the isolation and characterization of biologically active compounds from Thai marine animals, we found the Thai nudibranch J. funebris feeding on the blue sponge Xestospongia sp., growing around Sichang Island in the Gulf of Thailand. In this paper, we present the isolation, structure elucidation, and cytotoxicity of three stabilized bistetrahydroisoquinolines jorunnamycins A-C (1a-c) from the KCN-pretreated J. funebris. The preparation of a carbinolamine analog 1d from 1c and its chemical stability are also reported. Results and DiscussionJ. funebris (20 animals; 500 g, wet weight) was collected in the vicinity of Sichang Island at the depth of 3-5 m in March 2004 and its egg ribbons (23.2 g, wet weight) were separately obtained in November 2004. The animals were carefully dissected into two parts, the mantles and the visceral organs (the combined digestive glands and gonads). Then, the three parts were separately homogenized with phosphate buffer (pH 7). Aqueous KCN solution was added to each suspension, the mixture was macera...

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“…13) of sponge origin (Corley et al 1988;Quiñoà et al 1988) induced tubulin assembly in vitro (EC 50 = 4.3 μM). It arrested cell cycle of MDA-MB-435 cells at the G 2 /M phase with an IC 50 value of 5.7 nM, producing paclitaxel-like microtubule bundles (Mooberry et al 1999).…”

Section: Marine Toxins That Stabilize Microtubulesmentioning

confidence: 98%

Developmental Biology of Neoplastic Growth

Macieira‐Coelho¹

2005

Progress in Molecular and Subcellular Biology

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Laulimalides. New potent cytotoxic macrolides from a marine sponge and a nudibranch predator

Cited by 213 publications

References 0 publications

Synergistic Effects of Peloruside A and Laulimalide with Taxoid Site Drugs, but Not with Each Other, on Tubulin Assembly

Synergistic Effects of Peloruside A and Laulimalide with Taxoid Site Drugs, but Not with Each Other, on Tubulin Assembly

Jorunnamycins A-C, New Stabilized Renieramycin-Type Bistetrahydroisoquinolines Isolated from the Thai Nudibranch Jorunna funebris

Developmental Biology of Neoplastic Growth

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