Abstract
Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds.
Copyright © 2011. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antiprotozoal Agents / chemical synthesis
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Antiprotozoal Agents / chemistry
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Antiprotozoal Agents / pharmacology*
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Antiprotozoal Agents / therapeutic use*
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Berberine / chemical synthesis
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Berberine / chemistry
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Berberine / pharmacology*
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Berberine / therapeutic use
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Chlorocebus aethiops
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Disease Models, Animal
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Inhibitory Concentration 50
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Leishmania / drug effects
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Leishmaniasis / drug therapy
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Malaria / drug therapy
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Mice
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Models, Molecular
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Parasites / drug effects*
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Plasmodium falciparum / drug effects
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Protozoan Infections / drug therapy*
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Trypanosoma brucei brucei / drug effects
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Trypanosomiasis / drug therapy
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Vero Cells
Substances
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Antiprotozoal Agents
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Berberine