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Gametocytocidal and Sporontocidal Activity of Antimalarials against Plasmodium Berghei Anaka in Icr Mice and Anopheles Stephensi Mosquitoes

The gametocytocidal and sporontocidal activity of three 8-aminoquinolines (primaquine, WR-238605, and WR-242511), three dihydroacridine-diones (floxacrine, WR-250547, and WR-250548), a 1, 4-naphthoquinone (menoctone), a synthetic aminoalcohol (halofantrine), and a guanide (WR-182393) was determined against a cloned line of Plasmodium berghei ANKA. Gametocytocidal activity was assessed by treating mice with a single intraperitoneal inoculation of a given compound (25 mg base drug/kg mouse body weight) four days after the mice were infected with P. berghei. Thin blood smears were made every other day, and the percent parasitemia and macrogametocyte and microgametocyte rates were determined. Floxacrine, menoctone, WR-242511, WR-250547, and WR-250548 effectively cleared sexual and asexual parasites from the peripheral circulation within six days of drug administration. Halofantrine, primaquine, WR-182393, and WR-238605 were ineffective at clearing P. berghei ANKA from circulating erythrocytes at the doses tested; however, mice survival time increased markedly with these compounds when compared with the controls. Significant numbers of macrogametocytes and microgametocytes were present throughout the duration of the infection in mice treated with halofantrine, primaquine, WR-182393, and WR-238605. Sporontocidal activity was evaluated by allowing Anopheles stephensi mosquitoes to feed on P. berghei-infected mice 90 min after treatment with a particular drug. Halofantrine and WR-182393 exhibited no sporontocidal activity, while floxacrine, menoctone, primaquine, WR-238605, WR-242511, WR-250547, and WR-250548 exhibited significant activity. Minimum effective doses (mg base drug/kg of mouse body weight) that prevented mosquitoes from developing sporozoite-infected salivary glands were 0.1563 mg/kg for WR-250547, 0.625 mg/kg for menoctone, 1.25 mg/kg for primaquine, 10 mg/kg for floxacrine, 10 mg/kg for WR-242511, 10 mg/kg for WR-250548, and 25 mg/kg for WR-238605.

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