Abstract
In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2) via both oral and intravenous administration. In the transgenic adenocarcinoma of mouse prostate model, some of the trioxane dimers had potent anticancer activity.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma
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Administration, Oral
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Animals
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Antimalarials / chemical synthesis*
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Antimalarials / pharmacology
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Antimalarials / toxicity
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / toxicity
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Artemisinins / chemical synthesis*
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Artemisinins / pharmacology
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Artemisinins / toxicity
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Cell Line, Tumor
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Dimerization
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Drug Resistance
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Drug Screening Assays, Antitumor
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Flow Cytometry
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Injections, Intravenous
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Male
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Mice
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Plasmodium falciparum / drug effects
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Prostatic Neoplasms
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Structure-Activity Relationship
Substances
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Antimalarials
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Antineoplastic Agents
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Artemisinins