Abstract
Fluoroquinolones with pyrrolidinyl substitutions were tested against Trypanosoma brucei and mammalian cells. Bulky substituents at C-7 or a 1-2-bridging thiazolidine ring increased antitrypanosomal activity and selective toxicity. These compounds trap protein-DNA complexes and inhibit nucleic acid biosynthesis in trypanosomes, characteristics of topoisomerase II inhibition.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Anti-Infective Agents / chemical synthesis*
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Anti-Infective Agents / pharmacology*
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DNA / biosynthesis
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Fluoroquinolones
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Leukemia L1210 / parasitology
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Mice
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology*
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Structure-Activity Relationship
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Thymidine / metabolism
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Topoisomerase I Inhibitors
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Trypanocidal Agents / chemical synthesis*
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Trypanocidal Agents / pharmacology*
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Trypanosoma / drug effects*
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Trypanosoma / metabolism
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Trypanosoma brucei brucei / drug effects
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Tumor Cells, Cultured
Substances
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Anti-Infective Agents
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Fluoroquinolones
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Pyrrolidines
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Topoisomerase I Inhibitors
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Trypanocidal Agents
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DNA
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Thymidine