The Lithistida: important sources of compounds useful in biomedical research

Wright, Amy E.

doi:10.1016/j.copbio.2010.09.012

Cited by 10 publications

(12 citation statements)

References 48 publications

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“…[3] Lithistid sponges have proven to be a particularly fertile source [4] of such biologically relevant polyketide metabolites, including dictyostatin [5] and discodermolide. [5d,6] As part of a continued program aimed at the discovery of novel bioactive natural products from deep-water marine invertebrates, we have examined the relatively unexplored [7] lithistid sponge Leiodermatium .…”

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confidence: 99%

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Paterson

Dalby²,

Roberts

et al. 2011

Angew Chem Int Ed

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Leiodermatolide is a structurally unique macrolide, isolated from the deep-water marine sponge Leiodermatium sp., which exhibits potent antiproliferative activity against a range of human cancer cell lines (IC50 <10 nM) and dramatic effects on spindle formation in mitotic cells. Its unprecedented polyketide skeleton and stereochemistry were established using a combination of experimental and computational (DP4) NMR methods, and molecular modelling.

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confidence: 99%

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Paterson

Dalby²,

Roberts

et al. 2011

Angew Chem Int Ed

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“…[3] Lithistid sponges have proven to be a particularly fertile source [4] of such biologically relevant polyketide metabolites, including dictyostatin [5] and discodermolide. [5d, 6] As part of a continued program aimed at the discovery of novel bioactive natural products from deepwater marine invertebrates, we have examined the relatively unexplored [7] lithistid sponge Leiodermatium.…”

mentioning

confidence: 99%

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Paterson

Dalby²,

Roberts

et al. 2011

Angewandte Chemie

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Marine macrolides that selectively disrupt cell cycle events continue to occupy a central position as lead compounds in the ongoing search for novel anticancer agents, [1,2] highlighted by the recent FDA approval of Halaven (eribulin mesylate, a fully synthetic analogue of the halichondrins) for the treatment of advanced breast cancer. [3] Lithistid sponges have proven to be a particularly fertile source [4] of such biologically relevant polyketide metabolites, including dictyostatin [5] and discodermolide. [5d, 6] As part of a continued program aimed at the discovery of novel bioactive natural products from deepwater marine invertebrates, we have examined the relatively unexplored [7] lithistid sponge Leiodermatium. A crude extract of Leiodermatium sp. was found to exhibit substantial activity in an assay which identifies antimitotic agents through detection of phosphonucleolin, a marker of mitosis. [8] Bioassay-guided fractionation led to the isolation of leiodermatolide (1, Figure 1), whose unprecedented 16-membered macrolide skeleton, featuring an unsaturated side chain terminating in a d-lactone, has been elucidated through a combination of extensive NMR spectroscopic analysis, comparative DFT GIAO NMR shift calculations, and molecular modeling. Leiodermatolide was found to exhibit potent and selective antimitotic activity (IC 50 < 10 nm) against a range of human cancer cell lines by inducing G2/M cell cycle arrest, and represents a promising new lead for anticancer drug discovery.A specimen of Leiodermatium (1.04 kg) was collected at a depth of 401 m off the coast of Fort Lauderdale, Florida, using the Johnson Sea Link submersible. The frozen sponge was exhaustively extracted using a mixture of EtOAc/EtOH (9:1) followed by partitioning of the dried extract residue between EtOAc and H 2 O. Vacuum column chromatography of the organic partition on a silica gel stationary phase followed by reverse-phase HPLC of the active fraction led to the isolation of leiodermatolide (11.8 mg, 0.0011 % wet weight) as an amorphous white powder with ½a 24 D ¼À84.2 (c = 0.34, MeOH). [9] HRDART MS analysis of leiodermatolide (1) provided a [M+H] + ion at m/z 602.3705, appropriate for a molecular formula of C 34 H 51 NO 8 (calcd for [M+H], 602.3693, D = 1.2 mmu), requiring 10 sites of unsaturation. [10] Optimum NMR signal dispersion was realized in CD 2 Cl 2 ; inspection of the 13 C NMR spectrum revealed a total of 34 resonances in agreement with the HRMS formula. 13 C NMR resonances attributable to two ester groups (d C = 172.4, 170.4 ppm), one carbamate (d C = 157.6 ppm), and 10 olefinic carbons (d C = 137.9, 137.5, 134.2, 131.8, 130.0, 128.8, 128.5, 126.4, 125.9, 124.7 ppm) accounted for eight of the 10 sites of unsaturation, suggesting the presence of two rings.Interpretation of the 2D DQF-COSY spectrum coupled with the edited g-HSQC spectrum led to the assignment of seven isolated spin systems (A-G, Figure 2). These spin systems and their connectivity with the remaining atoms enabled assembly into the final planar struct...

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“…Moto purines and congeners are protein phosphatase inhibitors [27]. The complex polyketide swinholide A and bistheonellide A are biologically active metabolites that show nanomolar potent against tumor cells [6,7]. There are actin disrupting compounds derived from lithistida like kabiramide, sphinxolide and reidispongiolide, callipeltoside but these are not meant for commercial purposes [11,12].…”

Section: Commercially Available Biochemical Probes From Lithistid Spomentioning

confidence: 99%

“…Calyculin derived from the sponges Discodermia calyx has important key molecules for investigating cellular metabolism [2,6,62]. Moto purines and congeners are protein phosphatase inhibitors [27].…”

Section: Commercially Available Biochemical Probes From Lithistid Spomentioning

confidence: 99%

Lithistid Sponges Derived Compounds and Their Importance in Biological Research - A Review

Abirla

2018

Asian J Pharm Clin Res

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Lithistid sponges have an important source of complex natural compounds with biological activities. The lithistid sponges are of interest to biomedical science because of the great variety of pharmaceutically relevant biological activities of their chemical extracts and are considered as economically important. The compounds identified in these sponges have therapeutic potential and have been frequently hypothesized to contain compounds of bacterial origin. The peptides identified from these lithistid sponges are found to be the sources of antifungal activity. The active agents of these sponges also have cytotoxic and immunosuppressive activities. Many of the cyclic peptides of lithistid represent the anti-HIV activity. The different structure and biological activities of the compounds derived from these sponges have more chemical aspects too.

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The Lithistida: important sources of compounds useful in biomedical research

Cited by 10 publications

References 48 publications

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Leiodermatolide, a Potent Antimitotic Macrolide from the Marine Sponge Leiodermatium sp.

Lithistid Sponges Derived Compounds and Their Importance in Biological Research - A Review

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