engleski

Commercial Herbicides Screened for Toxicity in silico and Examined as Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

The widespread and frequent use of herbicides has led to the emergence of two major global issues: 1) increasing weed resistance to herbicides and 2) detrimental impact on health. A set of 509 herbicides collected from the literature and online databases was classified based on their modes of action and screened for toxic effects on human health based on predicted toxicities for in vitro and animal models and impact on environment. The analyses enabled us to estimate the toxicity profiles for herbicides of different herbicidal modes of action, including also their physicochemical properties (MW, TPSA, log P, log D, HBA, HBD, log BB, BBB penetration, etc.). We selected 11 compounds with potential neurotoxic effect for biological tests focusing on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes involved in neurotoxicity and detoxification mechanisms, respectively. Out of organophosphate herbicides (anilophos, piperophos, bensulide and butamiphos) and carbamates (flufenacet, desmedipham and phenmedipham), all of which exhibited an inhibition of both cholinesterases, anilophos was the most potent inhibitor of AChE (IC50=26 M) and BChE (8 M). Moreover, the inhibition of all of the listed herbicides was with a slight preference to bind BChE, which is known as a natural endogenous bioscavenger of various xenobiotics. The selected glyphosate, oxadiazon, tembotrione and terbuthylazine were poor inhibitors with an estimated IC50 above 1 mM. Our results given by in silico and in vitro analyses could give insight into the toxic effects of herbicides in use and may be the origin of new herbicides with less hazardous effects to humans and the environment. This research was supported by the Croatian Science Foundation (HrZZ-IP-2018-01-7683).

herbicides ; AChE ; BChE ; inhibition

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