Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta

J Org Chem. 2015 Aug 21;80(16):7849-55. doi: 10.1021/acs.joc.5b01264. Epub 2015 Aug 5.

Abstract

Bastimolide A (1), a polyhydroxy macrolide with a 40-membered ring, was isolated from a new genus of the tropical marine cyanobacterium Okeania hirsuta. This novel macrolide was defined by spectroscopy and chemical reactions to possess one 1,3-diol, one 1,3,5-triol, six 1,5-diols, and one tert-butyl group; however, the relationships of these moieties to one another were obscured by a highly degenerate (1)H NMR spectrum. Its complete structure and absolute configuration were therefore unambiguously determined by X-ray diffraction analysis of the nona-p-nitrobenzoate derivative (1d). Pure bastimolide A (1) showed potent antimalarial activity against four resistant strains of Plasmodium falciparum with IC50 values between 80 and 270 nM, although with some toxicity to the control Vero cells (IC50 = 2.1 μM), and thus represents a potentially promising lead for antimalarial drug discovery. Moreover, rigorous establishment of its molecular arrangement gives fresh insight into the structures and biosynthesis of cyanobacterial polyhydroxymacrolides.

Publication types

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

MeSH terms

  • Antimalarials / chemistry
  • Antimalarials / isolation & purification
  • Antimalarials / pharmacology*
  • Cyanobacteria / chemistry*
  • Drug Resistance
  • Macrolides / chemistry
  • Macrolides / isolation & purification
  • Macrolides / pharmacology*
  • Molecular Conformation
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Macrolides
  • bastimolide A