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Organic Chemistry 2018
Journal of Organic & Inorganic Chemistry
ISSN: 2472-1123
Page 23
August 16-17, 2018
Dublin, Ireland
6
th
Edition of International
Conference and Exhibition on
Organic Chemistry
L
igand-based or structure-based
in silico
methods, as well as
in vitro
methods were used for the evaluation of the inhibition
of
Mus musculus
and
Homo sapiens
acetylcholinesterase by
commercially available selected pesticides. Crystal structures
of simazine, monocrotophos, dimethoate, and acetamiprid
were used for the unconstrained conformational search with
various force fields (FFs) implemented in Monte Carlo/Multiple
Minimum (MC/MM) approach. Unconstrained conformational
searches were applied in the determination of intersynaptic
pre-bound conformations of other commonly used pesticides
(atrazine, propazine, carbofuran, carbaryl, tebufenozide,
imidacloprid, diuron, monuron, and linuron). Moreover,
energies of global minima, calculated with the best performing
FFs, were compared with selected pesticides toxicities against
Mus musculus
. For the majority of pesticides, low energies of
global minima in pre-bound states correlate with high toxicity.
The targeted pesticides are acetylcholinesterase (AChE)
inhibitors, so structure-based (SB) studies, in the form of
molecular docking and molecular dynamics (MD) on either
Mus
musculus
AChE (mAChE) or
Homo sapiens
AChE (hAChE), were
performed to predict their pharmacology. The mechanistic
pathways were established, and additionally confirmed by
QM DFT mechanistic studies, which can be further used in
the discovery of novel pesticides with desirable lower toxicity
against humans. We paid special attention to the mechanism
of hAChE inhibition by atrazine, propazine, and simazine. The
QM DFT (quantum mechanics – density functional theory)
mechanistic studies implied that atrazine, propazine, and
simazine could be considered as reversible hAChE inhibitors,
administered in high concentrations, and confirmed by
concentration-dependent kinetic studies of hAChE inhibition.
Biography
Biljana B Arsic pursued her PhD on the investigation of macrolide antibiotics
as anti-bacterial and potential anti-malarial medicines at The University of
Manchester, United Kingdom. She is a scientific associate in the department
of mathematics, faculty of sciences and mathematics, University of Nis, Re-
public of Serbia. She has published 37 papers in peer-reviewed journals in
english, two books in Serbian related to teaching, one chapter in the edited
book in english, and attended numerous conferences and symposia. She
worked as an associate editor, also was a member of the editorial board,
and is currently reviewer for numerous journals in english.
ba432@ymail.comSelected pesticides as acetylcholine esterase inhibitors:
theoretical and experimental studies
Biljana B Arsić
1,2
, Milan Mladenović
3
, Nevena Stanković
3
, Nezrina Mihović
3
,
Rino Ragno
4,5
Andrew Regan
2
, Jelena Milićević
6
, Tatjana M Trtić Petrović
6
and
Ružica Micić
7
1
University of Niš, Republic of Serbia
2
The University of Manchester, UK
3
University of Kragujevac, Republic of Serbia
4
Sapienza University of Rome, Italy
5
Alchemical Dynamics, Italy
6
Vinča Institute of Nuclear Sciences, University of Belgrade, Republic of Serbia
7
University of Priština, Republic of Serbia
Biljana B Arsić et al., J Org Inorg Chem 2018, Volume 4
DOI: 10.21767/2472-1123-C4-011