title: The survival times of malaria-infected mice are prolonged more by several new two-carbon-linked artemisinin-derived dimer carbamates than by the trioxane antimalarial drug artemether.
abstract: Sixteen new artemisinin-derived 2-carbon-linked trioxane dimers were prepared to study chemical structure/antimalarial activity relationships (SAR). Administering a very low single oral dose of only 5mg/kg of dimer secondary alcohol 6a or 6b plus 15 mg/kg of mefloquine hydrochloride prolonged the lives of Plasmodium berghei-infected mice to an average of 25 days after infection. This ACT chemotherapy result is of high medicinal significance because the antimalarial efficacy of the popular trioxane drug artemether (2) plus mefloquine under the same conditions was significantly lower (only 20 day average survival). NH-aryl carbamate derivatives 7e, 7i, and 7j of 2-carbon-linked dimer alcohol 6b also significantly outperformed artemether (2) in prolonging the survival times (25-27 days) of malaria-infected mice.
authors: Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
authors: Ryan C
authors: RC
authors: Conyers
authors: Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
authors: Jennifer R
authors: JR
authors: Mazzone
authors: Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
authors: Maxime A
authors: MA
authors: Siegler
authors: 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.
authors: Abhai K
authors: AK
authors: Tripathi
authors: 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.
authors: David J
authors: DJ
authors: Sullivan
authors: Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States.
authors: Bryan T
authors: BT
authors: Mott
authors: 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.
authors: Gary H
authors: GH
authors: Posner
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000077549:Artemether; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002219:Carbamates / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D002244:Carbon / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D004359:Drug Therapy, Combination; D008288:Malaria / Q000188:drug therapy / Q000401:mortality; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008968:Molecular Conformation; D010962:Plasmodium berghei / Q000187:drug effects; D013329:Structure-Activity Relationship; D016019:Survival Analysis
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002219:Carbamates; D002244:Carbon; C031327:artemisinin; D000077549:Artemether; D015767:Mefloquine
keywords: Antimalarial chemotherapy; Oral bioavailability; Single oral dose ACT; Trioxane dimer carbamates