1-Azaaurones derived from the naturally occurring aurones as potential antimalarial drugs.
We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic variation of the substituent at the B-ring revealed promising leads showing good activity on the CQ-resistant strain. In particular, 4,6-dimethoxy-4'-ethylazaaurone 22 showed antiplasmodial potency without noticeable toxicity. The easy synthesis of this family of compounds and the relevant antiplasmodial activity are in favor of promising candidates for further development.
Souard
Florence
F
Département de Pharmacochimie Moléculaire, Université de Grenoble I/CNRS, UMR 5063, 470 rue de la Chimie, BP 53 F-38041, Grenoble Cedex 9, France. florence.souard@ujf-grenoble.fr
Okombi
Sabrina
S
Beney
Chantal
C
Chevalley
Séverine
S
Valentin
Alexis
A
Boumendjel
Ahcène
A
D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000737:chemistry*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
C553184:(Z)-2-(4-ethylbenzylidene)-4,6-dimethoxy-2,3-dihydro-1H-indol-3-one; D000962:Antimalarials; D001372:Aza Compounds; D001572:Benzofurans; D007211:Indoles; C486837:aurone