Enhanced antimalarial activity of novel synthetic aculeatin derivatives.
We report the design, synthesis, and in vitro evaluation of novel polyspirocyclic structures, inspired by the antimalarial natural products, the aculeatins. A divergent synthetic strategy was conceived for the practical supply and has allowed the discovery of two novel and more potent analogues active on the Plasmodium falciparum 3D7 strain. Moreover, these compounds proved to be potent against Toxoplasma gondii. A number of features that govern these inhibitions were identified.
Peuchmaur
Marine
M
Département de Pharmacochimie Moléculaire, Université de Grenoble, CNRS UMR 5063, CNRS ICMG FR 2607, Bâtiment E, 470 Rue de la Chimie, F-38 041 Grenoble Cedex 9, France.
Saïdani
Nadia
N
Botté
Cyrille
C
Maréchal
Eric
E
Vial
Henri
H
Wong
Yung-Sing
YS
D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013141:Spiro Compounds / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000473:Alkanes; D000962:Antimalarials; D003512:Cyclohexanones; D013141:Spiro Compounds; C476177:aculeatin A; C476176:aculeatin B