title: New amide derivatives of quinoxaline 1,4-di-N-oxide with leishmanicidal and antiplasmodial activities.
abstract: Malaria and leishmaniasis are two of the World's most important tropical parasitic diseases. Continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-N-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum FCR-3 strain, Leishmania infantum and Leishmania amazonensis. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. The results obtained indicate that a cyclopentyl derivative had the best antiplasmodial activity (2.9 µM), while a cyclohexyl derivative (2.5 µM) showed the best activity against L. amazonensis, and a 3-chloropropyl derivative (0.7 µM) showed the best results against L. infantum. All these compounds also have a Cl substituent in the R⁷ position.
authors.affiliation: Unidad de Investigación y Desarrollo de Nuevos Medicamentos, Centro de Investigación en Farmacobiología Aplicada-CIFA, Universidad de Navarra, Pamplona 31080, Spain. cabareari@hotmail.com
authors.forename: Carlos
authors.initials: C
authors.lastname: Barea
authors.forename: Adriana
authors.initials: A
authors.lastname: Pabón
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
authors.forename: Silvia
authors.initials: S
authors.lastname: Galiano
authors.forename: German
authors.initials: G
authors.lastname: Gonzalez
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Eric
authors.initials: E
authors.lastname: Deharo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
mesh_terms: D000577:Amides / Q000737:chemistry; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000977:Antiparasitic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002522:Chlorocebus aethiops; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects; D010087:Oxides / Q000737:chemistry; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects; D011810:Quinoxalines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000577:Amides; D000962:Antimalarials; D000977:Antiparasitic Agents; D010087:Oxides; D011810:Quinoxalines