Antimalarial chemotherapy: artemisinin-derived dimer carbonates and thiocarbonates.
Several 2-carbon-linked trioxane dimer secondary alcohol carbonates 14 and thiocarbonates 15, combined with mefloquine and administered in a low single oral dose, prolonged the survival times of malaria-infected mice much more effectively than the popular monomeric antimalarial drug artemether plus mefloquine. Three dimer carbonates 14 and one dimer thiocarbonate 15 partially cured malaria-infected mice.
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
Jennifer R
JR
Mazzone
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
Ryan C
RC
Conyers
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States; The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States.
Abhai K
AK
Tripathi
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States; The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States.
David J
DJ
Sullivan
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States; The Johns Hopkins Malaria Research Institute, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21205, United States. Electronic address: ghp@jhu.edu.
Gary H
GH
Posner
D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D037621:Artemisinins / Q000737:chemistry*; D002254:Carbonates / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D019281:Dimerization; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010962:Plasmodium berghei / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
D000962:Antimalarials; D037621:Artemisinins; D002254:Carbonates; D013438:Sulfhydryl Compounds; C031327:artemisinin
Antimalarial chemotherapy; Oral bioavailability; Single oral dose ACT; Trioxane dimers