title: A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening.
abstract: 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.
authors.affiliation: DuPont Crop Protection, Stine-Haskell Research Center, 1094 Elkton Road, Newark, DE 19711, USA. michael.h.howard-1@usa.dupont.com
authors.forename: Michael H
authors.initials: MH
authors.lastname: Howard
authors.forename: Teodorica
authors.initials: T
authors.lastname: Cenizal
authors.forename: Steven
authors.initials: S
authors.lastname: Gutteridge
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Hanna
authors.forename: Yong
authors.initials: Y
authors.lastname: Tao
authors.forename: Maxim
authors.initials: M
authors.lastname: Totrov
authors.forename: Vernon A
authors.initials: VA
authors.lastname: Wittenbach
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Zheng
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008024:Ligands; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D000581:Amidohydrolases; C084507:peptide deformylase