Abstract
We developed a synthetic route to prepare isoquinoline analogs of the cancer drug clinical candidate tipifarnib. We show that these compounds kill Trypanosoma cruzi amastigotes grown in mammalian host cells at concentrations in the low nanomolar range. These isoquinolines represent new leads for the development of drugs to treat Chagas disease.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Chagas Disease / drug therapy
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Drug Evaluation, Preclinical
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Mice
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Molecular Conformation
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Parasitic Sensitivity Tests
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Quinolones / chemical synthesis
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Quinolones / chemistry
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Quinolones / pharmacology*
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Stereoisomerism
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Structure-Activity Relationship
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Trypanocidal Agents / chemical synthesis
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Trypanocidal Agents / chemistry
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Trypanocidal Agents / pharmacology*
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Trypanosoma cruzi / drug effects*
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Trypanosoma cruzi / growth & development
Substances
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Antineoplastic Agents
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Quinolones
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Trypanocidal Agents
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tipifarnib