The chemotherapy of rodent malaria, XXXVII. The in vivo action of two Mannich bases, WR 194,965 and WR 228,258 and an 8-aminoquinoline WR 225,448.
Two new Mannich base antimalarials, WR 194,965 and 228,258 exhibit blood schizontocidal action against Plasmodium berghei in vivo. This action is retained also against the P. berghei NS line which has a low level of resistance to chloroquine. While WR 228,258 is also active against the highly chloroquine-resistant RC line, WR 194,965 is not. Both compounds show slightly reduced activity against the highly mefloquine-resistant N/1100 line. WR 225,448, an 8-aminoquinoline, is as active against blood stages of the NS, RC and N/1100 lines of P. berghei as against the N strain, and more so on a dose/weight basis than the first two compounds. It shows a low level of cross-resistance against the primaquine-resistant P line. WR 225,448 has a clear causal prophylactic effect on the pre-erythrocytic schizonts of P. yoelii nigeriensis. While WR 194,965 and 228,258 also appeared to act on these stages, the effect is most probably due to residual action on emerging erythrocytic merozoites since pre-erythrocytic schizonts in treated animals were morphologically indistinguishable from those of the untreated control.
D000634:Aminoquinolines / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D001769:Blood / Q000469:parasitology; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D051379:Mice; D010961:Plasmodium
D000634:Aminoquinolines; D000962:Antimalarials; D002084:Butylated Hydroxytoluene; C044656:WR 194965; C044651:tebuquine; C044408:WR 225448