Malaria-infected mice are cured by a single oral dose of new dimeric trioxane sulfones which are also selectively and powerfully cytotoxic to cancer cells.
A new series of 6 dimeric trioxane sulfones has been prepared from the natural trioxane artemisinin in five or six chemical steps. One of these thermally and hydrolytically stable new chemical entities (4c) completely cured malaria-infected mice via a single oral dose of 144 mg/kg. At a much lower single oral dose of only 54 mg/kg combined with 13 mg/kg of mefloquine hydrochloride, this trioxane dimer 4c as well as its parent trioxane dimer 4b also completely cured malaria-infected mice. Both dimers 4c and 4b were potently and selectively cytotoxic toward five cancer cell lines.
Rosenthal
Andrew S
AS
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218-2685, USA.
Chen
Xiaochun
X
Liu
Jun O
JO
West
Diana C
DC
Hergenrother
Paul J
PJ
Shapiro
Theresa A
TA
Posner
Gary H
GH
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D037621:Artemisinins; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D004359:Drug Therapy, Combination; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D015767:Mefloquine / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*
D000962:Antimalarials; D000970:Antineoplastic Agents; D037621:Artemisinins; D013450:Sulfones; C031327:artemisinin; D015767:Mefloquine