title: 3-bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian.
abstract: A new fascaplysin analogue, 3-bromohomofascaplysin A (1), along with two known analogues, homofascaplysin A (2) and fascaplysin (3), were isolated from a Fijian Didemnum sp. ascidian. The absolute configurations of 3-bromohomofascaplysin A (1) and homofascaplysin A (2) were determined via experimental and theoretically calculated ECD spectra. The differential activities of 1-3 against different blood-borne life stages of the malaria pathogen Plasmodium falciparum were assessed. Homofascaplysin A (2) displayed an IC(50) of 0.55±0.11 nM against ring stage parasites and 105±38 nM against all live parasites. Given the stronger resistance of ring stage parasites against most current antimalarials relative to the other blood stages, homofascaplysin A (2) represents a promising agent for treatment of drug resistant malaria.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Lu
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ding
authors.forename: Xing-Cong
authors.initials: XC
authors.lastname: Li
authors.forename: Daignon R
authors.initials: DR
authors.lastname: Djigbenou
authors.forename: Brian T
authors.initials: BT
authors.lastname: Grimberg
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.forename: Chris M
authors.initials: CM
authors.lastname: Ireland
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Van Wagoner
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006842:Hydrocarbons, Brominated / Q000737:chemistry / Q000302:isolation & purification; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010963:Plasmodium falciparum / Q000187:drug effects; D014561:Urochordata / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines
chemical_list: D000962:Antimalarials; D006842:Hydrocarbons, Brominated; D007211:Indoles; C069346:fascaplysine; D000644:Quaternary Ammonium Compounds; D002243:Carbolines; D007212:Indolizines