TY  - JOUR
AU  - Mladenović, Milan P.
AU  - Arsić, Biljana
AU  - Stanković, Nevena M.
AU  - Mihović, Nezrina
AU  - Ragno, Rino
AU  - Regan, Andrew C.
AU  - Milićević, Jelena S.
AU  - Trtić-Petrović, Tatjana M.
AU  - Micić, Ružica J.
PY  - 2018
UR  - http://www.mdpi.com/1420-3049/23/9/2192
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/7862
AB  - Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (Eglob_min) and free energies of binding (∆Gbinding) were correlated with the pesticides’ acute toxicities (i.e., the LD50 values) against mice, as well to generate the model that could predict the LD50s against humans. Although for most of the pesticides the low Eglob_min correlates with the high acute toxicity, it is the ∆Gbinding that conditions the LD50 values for all the evaluated pesticides. Derived pLD50 = f(∆Gbinding) mAChE model may predict the pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.
T2  - Molecules
T1  - The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro
VL  - 23
IS  - 9
SP  - 2192
DO  - 10.3390/molecules23092192
ER  - 

@article{
author = "Mladenović, Milan P. and Arsić, Biljana and Stanković, Nevena M. and Mihović, Nezrina and Ragno, Rino and Regan, Andrew C. and Milićević, Jelena S. and Trtić-Petrović, Tatjana M. and Micić, Ružica J.",
year = "2018",
abstract = "Commercially available pesticides were examined as Mus musculus and Homo sapiens acetylcholinesterase (mAChE and hAChE) inhibitors by means of ligand-based (LB) and structure-based (SB) in silico approaches. Initially, the crystal structures of simazine, monocrotophos, dimethoate, and acetamiprid were reproduced using various force fields. Subsequently, LB alignment rules were assessed and applied to determine the inter synaptic conformations of atrazine, propazine, carbofuran, carbaryl, tebufenozide, imidacloprid, diuron, monuron, and linuron. Afterwards, molecular docking and dynamics SB studies were performed on either mAChE or hAChE, to predict the listed pesticides’ binding modes. Calculated energies of global minima (Eglob_min) and free energies of binding (∆Gbinding) were correlated with the pesticides’ acute toxicities (i.e., the LD50 values) against mice, as well to generate the model that could predict the LD50s against humans. Although for most of the pesticides the low Eglob_min correlates with the high acute toxicity, it is the ∆Gbinding that conditions the LD50 values for all the evaluated pesticides. Derived pLD50 = f(∆Gbinding) mAChE model may predict the pLD50 against hAChE, too. The hAChE inhibition by atrazine, propazine, and simazine (the most toxic pesticides) was elucidated by SB quantum mechanics (QM) DFT mechanistic and concentration-dependent kinetic studies, enriching the knowledge for design of less toxic pesticides.",
journal = "Molecules",
title = "The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro",
volume = "23",
number = "9",
pages = "2192",
doi = "10.3390/molecules23092192"
}

Mladenović, M. P., Arsić, B., Stanković, N. M., Mihović, N., Ragno, R., Regan, A. C., Milićević, J. S., Trtić-Petrović, T. M.,& Micić, R. J.. (2018). The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro. in Molecules, 23(9), 2192.
https://doi.org/10.3390/molecules23092192

Mladenović MP, Arsić B, Stanković NM, Mihović N, Ragno R, Regan AC, Milićević JS, Trtić-Petrović TM, Micić RJ. The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro. in Molecules. 2018;23(9):2192.
doi:10.3390/molecules23092192 .

Mladenović, Milan P., Arsić, Biljana, Stanković, Nevena M., Mihović, Nezrina, Ragno, Rino, Regan, Andrew C., Milićević, Jelena S., Trtić-Petrović, Tatjana M., Micić, Ružica J., "The Targeted Pesticides as Acetylcholinesterase Inhibitors: Comprehensive Cross-Organism Molecular Modelling Studies Performed to Anticipate the Pharmacology of Harmfulness to Humans In Vitro" in Molecules, 23, no. 9 (2018):2192,
https://doi.org/10.3390/molecules23092192 . .