Mixed tetraoxanes containing the acetone subunit as antimalarials

作者：Opsenica Dejan M; Terzic Natasa; Smith Philip L; Yang Youngsun; Anova Lalaine; Smith Kirsten S; Solaja Bogdan A^*

来源：Bioorganic & Medicinal Chemistry, 2008, 16(14): 7039-7045.

DOI：10.1016/j.bmc.2008.05.017

• mixed steroidal tetraoxanes
• cholic acid
• antimalarials
• antiproliferatives
• metabolic stability

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 GI(50), TGI, LC50 MG_MID 0.98 mu M, 3.80 mu M, 11.22 mu M, respectively. All tested compounds showed no toxic effects.

• 出版日期2008-7-15