Structure-activity relationship studies of the tricyclic indoline resistance-modifying agent.
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.
Department of Chemistry and Biochemistry, University of Colorado Boulder , Boulder, Colorado 80309, United States.
Le
L
Chang
Jessica D
JD
Podoll
Wei
W
Wang
Shane
S
Walls
Courtney P
CP
O'Rourke
Xiang
X
Wang
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000187:drug effects*; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D002227:Carbazoles; D007211:Indoles; C000589390:N-(2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl)-4-chlorobenzene-1-sulfonamide; D013449:Sulfonamides; C057812:indoline