title: The Bengamides: A Mini-Review of Natural Sources, Analogues, Biological Properties, Biosynthetic Origins, and Future Prospects.
abstract: 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.
authors.affiliation: Physical and Environmental Sciences Department, Colorado Mesa University , Grand Junction, Colorado 81501, United States.
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: White
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.
authors.forename: Karen
authors.initials: K
authors.lastname: Tenney
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Santa Cruz, California 95064, United States.
authors.forename: Phillip
authors.identifier: 0000-0002-9061-9549
authors.initials: P
authors.lastname: Crews
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D063208:Methionyl Aminopeptidases / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects; D011161:Porifera / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D001381:Azepines; D016328:NF-kappa B; C427480:bengamide B; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases