Design, synthesis and biological evaluation of organophosphorous-homodimers as dual binding site acetylcholinesterase inhibitors

Construction of an immobilised acetylcholinesterase column and its application in screening insecticidal constituents from Magnolia officinalis

“…34 The contents of 1 and 2 per 100 g of dried roots were calculated to be 65.8 ± 0.8 mg and 86.5 ± 1.1 mg respectively, with the recovery rate ranging from 86.7 to 94.2%. The IC 50 values of each inhibitor were determined to be 0.069 ± 0.008 mM (1) and 0.057 ± 0.015 mM (2). Under the same conditions, the positive wileyonlinelibrary.com/journal/ps control (huperzine A) possessed an IC 50 of 0.57 ± 0.16 μM, which was consistent with results of Cheng et al 35 As shown in the above HPLC and activity assay results, the two compounds, also represented by peaks 1 and 2, could be absorbed by AChE and had strong inhibition effects on AChE activity.…”

“…Target enzymes are extremely important in research and development of new pesticides . The most active pesticides target the crucial metabolic enzymes for insect metabolism . Acetylcholinesterase (AChE) is such a crucial enzyme, involved in neural transmission of insects and therefore a target of various neurotoxicants.…”

“…Then, the better method was combined with high-performance liquid chromatography (HPLC) to establish a model system that could rapidly detect and isolate insecticidal constituents from complex natural products. The above procedure was not only validated by the known inhibitor huperzine A but also used to screen and identify two compounds, magnolol (1) and honokiol (2), as AChE inhibitors from Houpu (Magnolia officinalis), which is a traditional Chinese herb. By using the bioassay method, we found that compound 2 showed a higher insecticidal activity against brown planthopper, Nilaparvata lugens (Stål), than the positive control chlorpyrifos, which was consistent with its crude AChE inhibitory activity and molecular docking experimental results.…”

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase

“…As described above, in addition to the active site, much attention has been focused on the importance of a site distal to the active site, known as the ‘peripheral binding site’, and inhibitors designed to interact with the active site and peripheral binding site in cholinesterases have been reported (Berg et al 2011; Nicolet et al 2003; Xie et al 2013; Zhao et al 2011). We are currently performing computational modeling studies to evaluate potential binding sites and to make predictions that can be tested experimentally using a larger library of compounds to dissect further the interactions important for binding.…”

Design, Synthesis and Biological Evaluation of α-Aminophosphonate Derivatives Containing a Pyrazole Moiety

“…6) Inhibition of AChE cannot lead to the hydrolysis of neurotransmitter ACh or accumulation of ACh in the synaptic cleft that results in that impeded neurotransmission is the primary mechanism of AChE inhibitors. [7][8][9][10] Especially, many organophosphorus pesticides (OPs) that serve as insecticides are AChE (EC 3.1.1.7) inhibitors that are widely used in agriculture [11][12][13] (Fig. 1).…”