engleski

Biological assessment of selected herbicides and pesticides in use as inhibitors of human cholinesterases and on HepG2 and SH-SY5Y cell lines

The toxicity of organophosphorus compounds (OPs) remains a major public health concern due to their widespread use as pesticides and herbicides. Their common mechanism of action involves the inhibition of enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), crucial for neurotransmission. Both chronic and acute poisoning by OPs can leave long-lasting health effects even when patients are treated with standard medical therapy. We investigated in silico and in vitro interactions and kinetics of inhibition for human cholinesterases with selected organophosphate pesticides and herbicides. Overall, the pesticides ethoprophos and fenamiphos and herbicides anilophos and piperophos were the most potent inhibitors of both cholinesterases, with a slight preference to bind BChE known as a natural endogeneous bioscavenger of various xenobiotics. Molecular modelling enabled an evaluation of interactions important for specificity and selectivity of inhibition. The tested compounds did not affect the viability of the cell lines upon 4, 24 and 48 hours of treatment and were not hepatotoxic or neurotoxic at concentrations in which they displayed inhibition activity. Based on overall results, the selected compounds may be the original structures for the design and synthesis of a new class of pesticides and herbicides safe for use, or even drugs for treatment of various neurodegenerative diseases. Acknowledgments: This work was supported by the Croatian Science Foundation (IP-2018-01-7683 and UIP-2017-05-7260).

Organophosphorus compounds, acetylcholinesterase, butyrylcholesterase, pesticides, herbicides

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