Chemical synthesis, in vitro acetohydroxyacid synthase (AHAS) inhibition, herbicidal activity, and computational studies of isatin derivatives

Wang, Jianguo, Tan, Haizhong, Li, Yonghong, Ma, Yi, Li, Zhengming and Guddat, Luke W. (2011) Chemical synthesis, in vitro acetohydroxyacid synthase (AHAS) inhibition, herbicidal activity, and computational studies of isatin derivatives. Journal of Agricultural and Food Chemistry, 59 18: 9892-9900. doi:10.1021/jf2021607


Author Wang, Jianguo
Tan, Haizhong
Li, Yonghong
Ma, Yi
Li, Zhengming
Guddat, Luke W.
Title Chemical synthesis, in vitro acetohydroxyacid synthase (AHAS) inhibition, herbicidal activity, and computational studies of isatin derivatives
Journal name Journal of Agricultural and Food Chemistry   Check publisher's open access policy
ISSN 0021-8561
1520-5118
Publication date 2011-09
Sub-type Article (original research)
DOI 10.1021/jf2021607
Volume 59
Issue 18
Start page 9892
End page 9900
Total pages 9
Place of publication Washington, DC, U.S.A.
Publisher American Chemical Society
Collection year 2012
Language eng
Formatted abstract
Acetohydroxyacid synthase (AHAS) catalyzes the first common step in the biosynthesis of the branched-chain amino acids. As a result of its metabolic importance in plants, it is a target for many commercial herbicides. Virtual screening analysis inspired the evaluation of 19 commercially available isatin analogues and 13 newly synthesized isatin derivatives as novel AHAS inhibitors and for their herbicidal activity. The best compound demonstrated 95% inhibition of the activity of Arabidopsis thaliana AHAS at a concentration of 100 mg L–1, whereas the herbicidal activities of three compounds reached 50% inhibition at a concentration of 10 mg L–1 using the rape root growth test. CoMFA contour models were established to understand the structure–activity relationships for this class of AHAS inhibitor. The compounds were docked to the active site cavity of A. thaliana AHAS using FlexX, and the dominant binding mode was consistent with frontier molecular orbital from DFT calculations. This is the first comprehensive study of isatin derivatives as AHAS inhibitors and provides a valuable starting point for the design of new herbicides.
Keyword AHAS
Rational design
Synthesis
Isatin derivatives
Biological activity
Herbicide
QSAR
Docking
DFT calculation
Molecular design
Sulfonylurea herbicides
Crystal-structures
Acetolactate synthase
Molecular docking
Site
Resistance
Binding
Density
Target
Plants
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Chemistry and Molecular Biosciences
 
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