Unbiased Screening of Marine Sponge Extracts for Anti-inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis

Q2 · BIOLOGY

Article

Author: Myers, Chad L. ; Andersen, Raymond J. ; Boone, Charlie ; Li, Sheena C. ; Schneiderman, Julia ; Woods, Kate ; Piotrowski, Jeff S. ; Victor, Rachel E. ; de Voogd, Nicole J. ; Sofiyev, Vladimir ; Fung, Shan-Yu ; Hirschfeld, Aaron F. ; Deshpande, Raamesh ; Turvey, Stuart E.

Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high-throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and -independent TLRs (i.e., TLR2, 3, 4, 5, and 7) and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation Factor 2 as the molecular target of girolline, which inhibits protein synthesis at the elongation step. Together these data identify the sponge natural product girolline as a potential anti-inflammatory agent acting through inhibition of protein synthesis.

23 Jun 2009·The Chemical RecordQ2 · CHEMISTRY

Antimalarial natural products of marine and freshwater origin

Q2 · CHEMISTRY

Review

Author: Joanna Kobylinska ; Karl Gademann

AbstractThis review highlights recently discovered antimalarial natural products from marine and freshwater sources described in the literature from 2006 to 2008. The structures as well as bioactivities of compounds against the malaria parasites such as Plasmodium falciparum are discussed, including, for example, agelasine, xestoquinone, alisiaquinone, crambescidin, venturamide, dragomabin, gragonamide, viridamide, salinosporamide, chaetoxanthone, nodulisporacid, tumonoic acid, girolline, oroidin, nostocarboline, aerucyclamide, and microcylamide 7806 and its revised structure. Synthetic derivatives of natural products are presented including plakortin, isoaaptamine, curcuphenol, pseudopyronine, manzamine, and nostocarboline. Consequences of these discoveries for the development of novel natural product agents against malaria are discussed. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 187–198; 2009: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.200900001

01 Aug 2008·Anti-Cancer Agents in Medicinal Chemistry

Clinical Status of Anti-Cancer Agents Derived from Marine Sources

Review

Author: Diwan S. Rawat ; Ram Singh ; Mukul Sharma ; Penny Joshi

The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 1	FR	-	-
Neoplasms	Phase 1	-	Sanofi	-

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