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 160mg/kg/day, while the anilide 9 exhibited MCD<or=20mg/kg/day. The diol 13 was most potent antiproliferative with GI(50), TGI, LC(50) MG_MID 0.98microM, 3.80microM, 11.22microM, respectively. All tested compounds showed no toxic effects.