title: Biological assay of a novel quinoxalinone with antimalarial efficacy on Plasmodium yoelii yoelii.
abstract: Compound 1-methyl-7-nitro-4-(5-(piperidin-1-yl)pentyl)-3,4-dihydroquinoxalin-2(1H)-one (VAM2-6) was evaluated against a blood-induced infection with chloroquine-sensitive Plasmodium yoelii yoelii lethal strain in CD1 mice in a 4-day test scheme. LD50 of the compound was 56.51 mg/kg and LD10 was 20.58 mg/kg (taken as the highest dose). Animals were treated by oral gavage of 20, 10, and 5 mg/kg. Mice in the untreated control group showed a progressively increasing parasitemia leading to mouse death on 6 days post-infection; in this group, all mice showed parasites in the blood on the fifth day of sampling; the mean parasitemia on that day was 19.4%. A 4-day dosage of 20 mg/kg of VAM2-6 showed a 97% chemosuppression of total parasitemia on the fifth day, a 28 days survival time, and 20% of cured animals. A 4-day dosage of 10 and 5 mg/kg showed 85 and 37%, respectively, chemosuppression of total parasitemia on the fifth day; but all mice died from days 6 to 9 post-infection with increasing parasitemia. Mice treated with chloroquine at 5 mg/kg survived during the experiment. The results obtained in this study showed that the infection outcome of P. yoelii yoelii-infected mice is affected by VAM2-6 compound by slowing down the parasite replication, retarding the patency time, and increasing their survival time. Although compound VAM2-6 was active at higher doses than chloroquine, these results leaves a door open to the study of its structure in order to improve its antimalarial activity.
authors: Laboratorio de Malariología, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, DF, 04510, Mexico. normariv@hotmail.com
authors: Norma
authors: N
authors: Rivera
authors: Yovani Marrero
authors: YM
authors: Ponce
authors: Vicente J
authors: VJ
authors: Arán
authors: Cecilia
authors: C
authors: Martínez
authors: Filiberto
authors: F
authors: Malagón
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001681:Biological Assay; D004195:Disease Models, Animal; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects*; D011810:Quinoxalines / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D011810:Quinoxalines