Deoxycholic acid-derived tetraoxane antimalarials and antiproliferatives(1).

Abstract

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.

• Authors: Natasa Terzić, Dejan Opsenica, Dragana Milić, Bernard Tinant, Kirsten S Smith, Wilbur K Milhous, Bogdan A Solaja
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 21 Pg. 5118-27 (Oct 18 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17887664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimalarials
• Antineoplastic Agents
• Cyclohexanes
• Tetraoxanes
• Deoxycholic Acid

Topics

• Animals
• Antimalarials (chemical synthesis, metabolism, pharmacology)
• Antineoplastic Agents (chemical synthesis, metabolism, pharmacology)
• Cell Line, Tumor
• Crystallography, X-Ray
• Cyclohexanes (chemical synthesis, metabolism, pharmacology)
• Deoxycholic Acid (analogs & derivatives, chemical synthesis, metabolism, pharmacology)
• Drug Resistance
• Drug Screening Assays, Antitumor
• Humans
• Malaria (drug therapy)
• Mice
• Microsomes (metabolism)
• Plasmodium berghei
• Plasmodium falciparum (drug effects)
• Stereoisomerism
• Structure-Activity Relationship
• Tetraoxanes (chemical synthesis, metabolism, pharmacology)