Combinatorial synthesis of substituted 3-(2-indolyl)piperidines and 2-phenyl indoles as inhibitors of ZipA-FtsZ interaction.
The ZipA-FtsZ protein-protein interaction is a potential target for antibacterial therapy. The design and parallel synthesis of a combinatorial library of small molecules, which target the FtsZ binding area on ZipA are described. Compounds were demonstrated to bind to the FtsZ binding domain of ZipA by HSQC NMR and to inhibit cell division in a cell elongation assay.
Jennings
Lee D
LD
Wyeth Research, Department of Medicinal Chemistry, 401 N. Middletown Road, Pearl River, NY 10965, USA. jenninl@wyeth.com <jenninl@wyeth.com>
Foreman
Kenneth W
KW
Rush
Thomas S
TS
Tsao
Desiree H H
DH
Mosyak
Lidia
L
Kincaid
Scott L
SL
Sukhdeo
Mohani N
MN
Sutherland
Alan G
AG
Ding
Weidong
W
Kenny
Cynthia Hess
CH
Sabus
Chantel L
CL
Liu
Hanlan
H
Dushin
Elizabeth G
EG
Moghazeh
Soraya L
SL
Labthavikul
Pornpen
P
Petersen
Peter J
PJ
Tuckman
Margareta
M
Haney
Steven A
SA
Ruzin
Alexey V
AV
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry*; D018797:Cell Cycle Proteins / Q000737:chemistry*; D002455:Cell Division / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D029968:Escherichia coli Proteins / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029968:Escherichia coli Proteins; C076835:FtsZ84 protein, E coli; D007211:Indoles; D010880:Piperidines; C103795:ZipA protein, E coli