3-bromohomofascaplysin A, a fascaplysin analogue from a Fijian Didemnum sp. ascidian

Bioorg Med Chem. 2011 Nov 15;19(22):6604-7. doi: 10.1016/j.bmc.2011.05.046. Epub 2011 Jun 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimalarials / chemistry
  • Antimalarials / isolation & purification
  • Antimalarials / pharmacology
  • Hydrocarbons, Brominated / chemistry
  • Hydrocarbons, Brominated / isolation & purification
  • Indoles / chemistry*
  • Indoles / isolation & purification
  • Indoles / pharmacology
  • Molecular Conformation
  • Nuclear Magnetic Resonance, Biomolecular
  • Plasmodium falciparum / drug effects
  • Urochordata / chemistry*

Substances

  • Antimalarials
  • Hydrocarbons, Brominated
  • Indoles
  • fascaplysine