deoxycholic-acid and Malaria

The synthesis of deoxycholic acid (DCA)- and cholic acid (CA)-derived mixed tetraoxanes revealed that N-(2-dimethylamino)ethyl derivatives are potent antimalarials in vitro and in vivo. The tetraoxanes presented in this paper are dual inhibitors: besides curing mice in vivo without observed toxic effects, they kill cancer cell lines at very low concentrations. For example, DCA and CA derivatives 16 and 25 cured 3/5 (160 mg/kg/day) and 2/5 (40 mg/kg/day, MTD >960 mg/kg), respectively, and they were extremely active against melanoma LOX IMVI cancer, LC50 = 22 nM and 69 nM, respectively.

Topics: Animals; Antimalarials; Antineoplastic Agents; Cell Line, Tumor; Crystallography, X-Ray; Cyclohexanes; Deoxycholic Acid; Drug Resistance; Drug Screening Assays, Antitumor; Humans; Malaria; Mice; Microsomes; Plasmodium berghei; Plasmodium falciparum; Stereoisomerism; Structure-Activity Relationship; Tetraoxanes