Bastimolide A, a Potent Antimalarial Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania hirsuta.
J Org Chem
; 80(16): 7849-55, 2015 Aug 21.
Article
en En
| MEDLINE
| ID: mdl-26222145
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Cianobacterias
/
Macrólidos
/
Antimaláricos
Idioma:
En
Revista:
J Org Chem
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos