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The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects

[Image: see text] This review focuses entirely on the natural bengamides and selected synthetic analogues that have inspired decades of research. Bengamide A was first reported in 1986 from the sponge Jaspis cf. coriacea, and bengamide-containing sponges have been gathered from many biogeographic si...

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Autores principales: White, Kimberly N., Tenney, Karen, Crews, Phillip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society and American Society of Pharmacognosy 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368688/
https://www.ncbi.nlm.nih.gov/pubmed/28185457
http://dx.doi.org/10.1021/acs.jnatprod.6b00970
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author White, Kimberly N.
Tenney, Karen
Crews, Phillip
author_facet White, Kimberly N.
Tenney, Karen
Crews, Phillip
author_sort White, Kimberly N.
collection PubMed
description [Image: see text] This review focuses entirely on the natural bengamides and selected synthetic analogues that have inspired decades of research. Bengamide A was first reported in 1986 from the sponge Jaspis cf. coriacea, and bengamide-containing sponges have been gathered from many biogeographic sites. In 2005, a terrestrial Gram-negative bacterium, Myxococcus virescens, was added as a source for bengamides. Biological activity data using varying bengamide-based scaffolds has enabled fine-tuning of structure–activity relationships. Molecular target finding contributed to the creation of a synthetic “lead” compound, LAF389, that was the subject of a phase I anticancer clinical trial. Despite clinical trial termination, the bengamide compound class is still attracting worldwide attention. Future breakthroughs based on the bengamide scaffold are possible and could build on their nanomolar in vitro and positive in vivo antiproliferative and antiangiogenic properties. Bengamide molecular targets include methionine aminopeptidases (MetAP1 and MetAP2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). A mixed PKS/NRPS biosynthetic gene cluster appears to be responsible for creation of the bengamides. This review highlights that the bengamides have driven inspirational studies and that they will remain relevant for future research, even 30 years after the discovery of the first structures.
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spelling pubmed-53686882017-03-29 The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects White, Kimberly N. Tenney, Karen Crews, Phillip J Nat Prod [Image: see text] This review focuses entirely on the natural bengamides and selected synthetic analogues that have inspired decades of research. Bengamide A was first reported in 1986 from the sponge Jaspis cf. coriacea, and bengamide-containing sponges have been gathered from many biogeographic sites. In 2005, a terrestrial Gram-negative bacterium, Myxococcus virescens, was added as a source for bengamides. Biological activity data using varying bengamide-based scaffolds has enabled fine-tuning of structure–activity relationships. Molecular target finding contributed to the creation of a synthetic “lead” compound, LAF389, that was the subject of a phase I anticancer clinical trial. Despite clinical trial termination, the bengamide compound class is still attracting worldwide attention. Future breakthroughs based on the bengamide scaffold are possible and could build on their nanomolar in vitro and positive in vivo antiproliferative and antiangiogenic properties. Bengamide molecular targets include methionine aminopeptidases (MetAP1 and MetAP2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). A mixed PKS/NRPS biosynthetic gene cluster appears to be responsible for creation of the bengamides. This review highlights that the bengamides have driven inspirational studies and that they will remain relevant for future research, even 30 years after the discovery of the first structures. American Chemical Society and American Society of Pharmacognosy 2017-02-10 2017-03-24 /pmc/articles/PMC5368688/ /pubmed/28185457 http://dx.doi.org/10.1021/acs.jnatprod.6b00970 Text en Copyright © 2017 American Chemical Society and American Society of Pharmacognosy This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle White, Kimberly N.
Tenney, Karen
Crews, Phillip
The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title_full The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title_fullStr The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title_full_unstemmed The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title_short The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects
title_sort bengamides: a mini-review of natural sources, analogues, biological properties, biosynthetic origins, and future prospects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368688/
https://www.ncbi.nlm.nih.gov/pubmed/28185457
http://dx.doi.org/10.1021/acs.jnatprod.6b00970
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