Mixed tetraoxanes containing the acetone subunit as antimalarials

Abstract

Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi-drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160 mg/kg/day, while the anilide 9 exhibited MCD ≤ 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI50, TGI, LC50 MG_MID 0.98 μM, 3.80 μM, 11.22 μM, respectively. All tested compounds showed no toxic effects.