Synthesis and antimalarial activity of new 3-arylquinoxaline-2-carbonitrile derivatives.
New series of 3-arylquinoxaline-carbonitrile derivatives have been synthesized from various 5-substituted or 5,6-disubstituted benzofuroxanes and tested for their in vitro and in vivo activity against the erythrocytic development of Plasmodium falciparum strain with different chloroquine-resistance status. Quinoxaline 1,4-dioxide derivatives showed superior antimalarial activity in respect to reduced quinoxaline analogues. The best activity was observed with nonsubstituted quinoxaline 1,4-dioxides in positions 6 and 7 of the aromatic ring and with a hydrogen or chloro substituent in para position of the phenyl group.
Zarranz
Belén
B
Unidad en Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada CIFA, Universidad de Navarra, Pamplona Spain.
Jaso
Andrés
A
Aldana
Ignacio
I
Monge
Antonio
A
Maurel
Séverine
S
Deharo
Eric
E
Jullian
Valérie
V
Sauvain
Michel
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006427:Hemin / Q000378:metabolism; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D009570:Nitriles / Q000494:pharmacology*; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D007202:Indicators and Reagents; D009570:Nitriles; D011810:Quinoxalines; D006427:Hemin