Abstract
Previously we discovered a tricyclic indoline, N-[2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl]-4-chlorobenzene-1-sulfonamide (1, Of1), from bioinspired synthesis of a highly diverse polycyclic indoline alkaloid library, that selectively resensitizes methicillin-resistant Staphylococcus aureus strains to β-lactam antibiotics. Herein, we report a thorough structure-activity relationship investigation of 1, which identified regions of 1 that tolerate modifications without compromising activity and afforded the discovery of a more potent analogue with reduced mammalian toxicity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology*
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Carbazoles / pharmacology*
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Drug Resistance, Microbial / drug effects*
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HeLa Cells
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Hemolysis / drug effects
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Humans
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Indoles / chemistry
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Indoles / pharmacology*
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Magnetic Resonance Spectroscopy
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Microbial Sensitivity Tests
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Spectrometry, Mass, Electrospray Ionization
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Structure-Activity Relationship
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Sulfonamides / pharmacology*
Substances
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Anti-Bacterial Agents
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Carbazoles
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Indoles
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N-(2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl)-4-chlorobenzene-1-sulfonamide
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Sulfonamides
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indoline