Bis-isoquinolinium and bis-pyridinium acetylcholinesterase inhibitors: in vitro screening of probes for novel selective insecticides†
Insects have a huge impact on quality of life around the world. They play roles in transmitting diseases, crop-destruction, and as residential pests. Their increased resistance to the existing pesticides and the toxicity of carbamates (CA) and organophosphates (OP) has led to the development of new environmentally safe insecticides. In our study, thirty different bis-isoquinolinium and bis-pyridinium acetylcholinesterase inhibitors were tested as candidates for potential new selective pesticides. Our compounds were evaluated in vitro on insect acetylcholinesterase (AChE) from Musca domestica and human erythrocyte AChE using the modified Ellman's method. The values of IC50 were compared and expressed via a selectivity index (SI) towards the insect enzyme. K299, K416, and K423 provided a high SI and seem to be suitable as new lead structures of novel selective anticholinesterase insecticides. Docking studies further provided the rational background uncovering the disparities in the ligand–enzyme binding modes for each AChE enzyme. In vitro assessments as well as docking studies highlighted K299 and K416 as suitable candidates for lead structures of novel pesticides. However, further evaluation is needed to confirm this statement.