Synthesis and antiplasmodial activity of 3-furyl and 3-thienylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives.
The aim of this study was to identify new compounds active against Plasmodium falciparum based on our previous research carried out on 3-phenyl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives. Twelve compounds were synthesized and evaluated for antimalarial activity. Eight of them showed an IC(50) less than 1 microM against the 3D7 strain. Derivative 1 demonstrated high potency (IC(50)= 0.63 microM) and good selectivity (SI=10.35), thereby becoming a new lead-compound.
Vicente
Esther
E
Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), University of Navarra, 31080 Pamplona, Spain.
Charnaud
Sarah
S
Bongard
Emily
E
Villar
Raquel
R
Burguete
Asunción
A
Solano
Beatriz
B
Ancizu
Saioa
S
Pérez-Silanes
Silvia
S
Aldana
Ignacio
I
Vivas
Livia
L
Monge
Antonio
A
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004351:Drug Resistance / Q000187:drug effects; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010087:Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C526930:3-thienylquinoxaline-2-carbonitrile 1,4-di-N-oxide; D000962:Antimalarials; D003497:Cyclic N-Oxides; D009570:Nitriles; D010087:Oxides; D011810:Quinoxalines