A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening.
Peptide deformylase (PDF) has been identified as a promising antibacterial and herbicide target. A structurally novel class of inhibitors containing a 2-thioxo-thiazolidin-4-one heterocycle substituted by an arylidene group at the 5-position and a hexanoic acid side chain at the 3-position was discovered independently via high-throughput screening and virtual ligand screening. Data mining and analogue synthesis established a structure--activity relationship for the side chain region that is consistent with the docked structure.
Howard
Michael H
MH
DuPont Crop Protection, Stine-Haskell Research Center, 1094 Elkton Road, Newark, DE 19711, USA. michael.h.howard-1@usa.dupont.com
Cenizal
Teodorica
T
Gutteridge
Steven
S
Hanna
Wayne S
WS
Tao
Yong
Y
Totrov
Maxim
M
Wittenbach
Vernon A
VA
Zheng
Ya-Jun
YJ
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D008024:Ligands; D000581:Amidohydrolases; C084507:peptide deformylase