Abstract
Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has already been reported. As a consequence, novel chemotypes are urgently needed. Herein we report a novel, in vivo active, fast-acting antimalarial chemotype based on a benzimidazole core. This discovery is the result of a medicinal chemistry plan focused on improving the developability profile of an antichlamydial chemical class previously reported by our group.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / chemical synthesis
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Amides / pharmacokinetics
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Amides / pharmacology
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Animals
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Antimalarials / chemical synthesis*
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Antimalarials / pharmacokinetics
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Antimalarials / pharmacology*
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Benzamides / chemical synthesis*
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Benzamides / pharmacokinetics
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Benzamides / pharmacology*
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Benzimidazoles / chemical synthesis*
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Benzimidazoles / chemistry*
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Benzimidazoles / pharmacokinetics
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Benzimidazoles / pharmacology*
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Cell Proliferation / drug effects*
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Cells, Cultured
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Drug Design*
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
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Female
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Humans
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Malaria, Falciparum
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Mice, Inbred NOD
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Mice, SCID
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Models, Molecular
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Molecular Structure
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Plasmodium falciparum
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Structure-Activity Relationship
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Tissue Distribution
Substances
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Amides
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Antimalarials
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Benzamides
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Benzimidazoles
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels