Synthesis and antiplasmodial activity of 3-furyl and 3-thienylquinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives

• Published in: Molecules (Basel, Switzerland) Vol. 13; no. 1; pp. 69 - 77
• Main Authors: Vicente, Esther, Charnaud, Sarah, Bongard, Emily, Villar, Raquel, Burguete, Asunción, Solano, Beatriz, Ancizu, Saioa, Pérez-Silanes, Silvia, Aldana, Ignacio, Vivas, Livia, Monge, Antonio
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.01.2008; MDPI
• Subjects: Animals; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Antiparasitic agents; antiplasmodial; Cell Death - drug effects; Cell Line; Cyclic N-Oxides - chemical synthesis; Cyclic N-Oxides - chemistry; Cyclic N-Oxides - pharmacology; Cytotoxicity; Drug Resistance - drug effects; Malaria; N-oxides; Nitriles - chemical synthesis; Nitriles - chemistry; Nitriles - pharmacology; Oxides - chemical synthesis; Oxides - chemistry; Oxides - pharmacology; P. falciparum; Parasitic Sensitivity Tests; Plasmodium falciparum - drug effects; Quinoxaline; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; Tropical diseases
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules13010069

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.