Design, Synthesis, and Biological Evaluation of Hexacyclic Tetracyclines as Potent, Broad Spectrum Antibacterial Agents.
A series of novel hexacyclic tetracycline analogues ("hexacyclines") was designed, synthesized, and evaluated for antibacterial activity against a wide range of clinically important bacteria isolates, including multidrug-resistant, Gram-negative pathogens. Valuable structure-activity relationships were identified, and several hexacyclines displayed potent, broad spectrum antibacterial activity, including promising anti-Pseudomonas aeruginosa activity in vitro and in vivo.
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Cuixiang
C
Sun
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Diana K
DK
Hunt
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Chi-Li
CL
Chen
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Yonghong
Y
Deng
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Minsheng
M
He
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Roger B
RB
Clark
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Corey
C
Fyfe
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Trudy H
TH
Grossman
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Joyce A
JA
Sutcliffe
†Discovery Chemistry, ‡Microbiology, Tetraphase Pharmaceuticals, 480 Arsenal Street, Watertown, Massachusetts 02472, United States.
Xiao-Yi
XY
Xiao
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D015195:Drug Design; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013754:Tetracyclines / Q000494:pharmacology*; D013848:Thigh / Q000382:microbiology
D000900:Anti-Bacterial Agents; D013754:Tetracyclines