The chemotherapy of rodent malaria. LI. Studies on a new 8-aminoquinoline, WR 238,605.

WR 238,605, a novel 3-phenoxy-substituted 8-aminoquinoline, possesses causal prophylactic, blood schizontocidal and gametocytocidal activity against rodent malaria parasites. Against the asexual, intra-erythrocytic stages of drug-sensitive Plasmodium berghei N strain, it is about nine times as active as primaquine (PQ). It is from four to 100 times as active as PQ against lines of P. berghei or P. yoelii that are resistant to currently used antimalarials. WR 238,605 is three times as active as PQ against the pre-erythrocytic stages of P. y. nigeriensis but it has very poor gametocytocidal action and no sporontocidal activity against this parasite. In combination with chloroquine (CQ), WR 238,605 and PQ display a synergistic or 'resistance-reversing' action against CQ-resistant P. yoelii NS parasites. No such effects are seen when WR 238,605 is deployed with mefloquine against a mefloquine-resistant line or with artemisinin against an artemisinin-resistant line and it appears to be antagonistic to halofantrine against a halofantrine-resistant parasite. It is suggested that WR 238,605 is a good candidate compound for clinical trials against polyresistant P. falciparum, possibly in combination with CQ.