title: Identification of some novel AHAS inhibitors via molecular docking and virtual screening approach.
abstract: Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) catalyzes the first common step in branched-chain amino acid biosynthesis. This enzyme is an important target for the design of environmental-benign herbicides. Based on the crystal structure of AHAS/sulfonylurea complex, we have carried out computational screening of the ACD-3D database in order to look for novel non-sulfonylurea inhibitors of AHAS for the first time. Three novel compounds were found to inhibit plant AHAS in vitro among 14 procured compounds. One compound showed promising activity in vivo for rape root growth inhibition bioassay. This research provided useful clues for further design and discovery of AHAS inhibitors.
authors.affiliation: State-Key Laboratory of Elemento-Organic Chemistry, National Pesticide Engineering Research Center, Nankai University, Tianjin 300071, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Xiao
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Li
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D017360:Arabidopsis / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D001665:Binding Sites; D001681:Biological Assay; D029741:Brassica rapa / Q000187:drug effects / Q000254:growth & development; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006540:Herbicides / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D008970:Molecular Weight; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006540:Herbicides; D008024:Ligands; D000095:Acetolactate Synthase