An enantiomer-based virtual screening approach: Discovery of chiral organophosphates as acetyl cholinesterase inhibitors.

@article{Zhang2017AnEV,
  title={An enantiomer-based virtual screening approach: Discovery of chiral organophosphates as acetyl cholinesterase inhibitors.},
  author={Aiqian Zhang and Yunsong Mu and Fengchang Wu},
  journal={Ecotoxicology and environmental safety},
  year={2017},
  volume={138},
  pages={
          215-222
        }
}
Chiral organophosphates (OPs) have been used widely around the world, very little is known about binding mechanisms with biological macromolecules. An in-depth understanding of the stereo selectivity of human AChE and discovering bioactive enantiomers of OPs can decrease health risks of these chiral chemicals. In the present study, a flexible molecular docking approach was conducted to investigate different binding modes of twelve phosphorus enantiomers. A pharmacophore model was then developed… 
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References

SHOWING 1-10 OF 45 REFERENCES
Enantioselective interaction with acetylcholinesterase of an organophosphate insecticide fenamiphos.
Enantioselectivity in the environmental behavior and ecotoxicity of chiral pesticide is widely observed. However, the investigation of the enantioselective mechanisms remains limited. In this study,
A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs
  • Sehan Lee, M. Barron
  • Chemistry, Computer Science
    Journal of Computer-Aided Molecular Design
  • 2016
TLDR
The combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.
Molecular Docking, Metal Substitution and Hydrolysis Reaction of Chiral Substrates of Phosphotriesterase.
TLDR
This work aims to study the interaction mode between the PTE enzyme and organophosphorus compounds, in which Sarin, Soman, Tabun and VX have been used, which are potent acetylcholinesterase inhibitors, taking into account the enantiomers "Rp" and " Sp" of each compound, with the Sp-enantiomers presenting the higher toxicity.
Enantioselective interaction of acid α-naphthyl acetate esterase with chiral organophosphorus insecticides.
TLDR
The observations indicated α-naphthyl acetate esterase (ANAE) and AChE have similar selective inhibition kinetics and postinhibitory reactions in reaction with chiral OPs.
Improvement of enantioselectivity of chiral organophosphate insecticide hydrolysis by bacterial phosphotriesterase
TLDR
This work attempted to alter the enantioselectivity of PTE in order to degrade toxic EPN enantiomer effectively, and found that PTE preferred R-EPN over S-EPn in the presence of DMSO by a factor of 2.
Exploring the active center of human acetylcholinesterase with stereomers of an organophosphorus inhibitor with two chiral centers.
The stereoselectivity of the phosphonylation reaction and the effects of adduct configuration on the aging process were examined for human acetylcholinesterase (HuAChE) and its selected active center
Chromatographic preparation and kinetic analysis of interactions between tabun enantiomers and acetylcholinesterase.
TLDR
The results show a large difference in the inhibitory potency between (-)- and (+)-tabun and provide further insight into the kinetic interactions between tabun enantiomers and AChE and may contribute to the development of more effective treatment options.
Stereoselective hydrolysis of organophosphate nerve agents by the bacterial phosphotriesterase.
TLDR
A series of enantiomerically pure chiral nerve agent analogues containing the relevant phosphoryl centers found in GB, GD, GF, VX, and VR has been developed and accurately predicts the improved activity and stereoselectivity against the authentic nerve agents used in this study.
Development of 3D-QSAR Model for Acetylcholinesterase Inhibitors Using a Combination of Fingerprint, Molecular Docking, and Structure-Based Pharmacophore Approaches.
  • Sehan Lee, M. Barron
  • Chemistry, Medicine
    Toxicological sciences : an official journal of the Society of Toxicology
  • 2015
TLDR
A 3D-fingerprint descriptor encoding protein-ligand interactions was developed using molecular docking and structure-based pharmacophore to rationalize the structural requirements responsible for the activity of AChEIs and revealed that the compounds with high inhibition potency had proper conformation in the active site gorge and interacted with key amino acid residues.
Separation and aquatic toxicity of enantiomers of the organophosphorus insecticide trichloronate.
TLDR
Assessment of the environmental safety of chiral OPs should take stereospecificity into consideration, after significant differences were found between the enantiomers in acute aquatic toxicity to Ceriodaphnia dubia and Daphnia magna.
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