Mixed tetraoxanes containing the acetone subunit as antimalarials
AuthorsOpsenica, Dejan M.
Smith, Philip L.
Smith, Kirsten S.
Šolaja, Bogdan A.
Article (Published version)
MetadataShow full item record
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 lt = 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. (c) 2008 Elsevier Ltd. All rights reserved.
Keywords:mixed steroidal tetraoxanes / cholic acid / antimalarials / antiproliferatives / metabolic stability
Source:Bioorganic and Medicinal Chemistry, 2008, 16, 14, 7039-7045
- Pergamon-Elsevier Science Ltd, Oxford