Abstract
The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolated from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastraceae) on the reversion of the resistant phenotype on a multidrug-resistant Leishmania line and their binding to recombinant C-terminal nucleotide-binding domain of Leishmania P-glycoprotein-like transporter were studied. The structures of the new compounds (1-5) were elucidated by spectroscopic methods, including (1)H-(13)C heteronuclear correlation (HMQC), long-range correlation spectra with inversal detection (HMBC), ROESY experiments, and chemical correlations. The absolute configuration of one of them (1) was determined by CD studies. The structure-activity relationship is discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Animals
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Antibiotics, Antineoplastic / pharmacology*
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Circular Dichroism
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Daunorubicin / pharmacology*
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Drug Resistance, Multiple
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Escherichia coli / metabolism
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Leishmania tropica / drug effects*
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Leishmania tropica / metabolism
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Protein Binding
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Rosales / chemistry*
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Sesquiterpenes / chemical synthesis*
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Sesquiterpenes / chemistry
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Sesquiterpenes / metabolism
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Sesquiterpenes / pharmacology
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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 / metabolism
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Trypanocidal Agents / pharmacology
Substances
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8-acetoxy-9-benzoyloxy-15(2)-methylbutyroyloxy-2-nicotynoyloxy-1,4,6-trihydroxydihydro-beta-agarofuran
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibiotics, Antineoplastic
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Sesquiterpenes
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Trypanocidal Agents
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Daunorubicin