title: Dragonamide E, a modified linear lipopeptide from Lyngbya majuscula with antileishmanial activity.
abstract: Tropical parasitic and infectious diseases, such as leishmaniasis, pose enormous global health threats, but are largely neglected in commercial drug discovery programs. However, the Panama International Cooperative Biodiversity Group (ICBG) has been working to identify novel treatments for malaria, Chagas' disease, and leishmaniasis through an investigation of plants and microorganisms from Panama. We have pursued activity-guided isolation from an extract of Lyngbya majuscula that was found to be active against leishmaniasis. A new modified linear peptide from the dragonamide series was isolated, dragonamide E (1), along with two known modified linear peptides, dragonamide A (2) and herbamide B (3). Dragonamides A and E and herbamide B exhibited antileishmanial activity with IC50 values of 6.5, 5.1, and 5.9 microM, respectively. Spectroscopic and stereochemical data for dragonamide E (1) and herbamide B (3; the spectroscopic and stereochemical data for this substance is incomplete in the literature) are presented as well as comparisons of biological activity within the dragonamide compound family. Biosynthetic differences among marine compounds with a terminal free amide are also discussed.
authors.affiliation: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Marcy J
authors.initials: MJ
authors.lastname: Balunas
authors.forename: Roger G
authors.initials: RG
authors.lastname: Linington
authors.forename: Kevin
authors.initials: K
authors.lastname: Tidgewell
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Fenner
authors.forename: Luis-David
authors.initials: LD
authors.lastname: Ureña
authors.forename: Gina Della
authors.initials: GD
authors.lastname: Togna
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects; D020128:Inhibitory Concentration 50; D007893:Leishmania donovani / Q000187:drug effects*; D008235:Lyngbya Toxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents; D008235:Lyngbya Toxins; D009842:Oligopeptides; C547100:dragonamide E; D002738:Chloroquine