Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives(1).
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.
Terzić
Natasa
N
Institute of Chemistry, Technology and Metallurgy, Belgrade, Serbia.
Opsenica
Dejan
D
Milić
Dragana
D
Tinant
Bernard
B
Smith
Kirsten S
KS
Milhous
Wilbur K
WK
Solaja
Bogdan A
BA
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045568:Tetraoxanes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D000962:Antimalarials; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D045568:Tetraoxanes; D003840:Deoxycholic Acid