Molecular modeling of acetylcholinesterase interaction with irreversible and reversible organophosphorous inhibitors

Abstract

Three-dimensional Quantitative Structure-Аctivity Relationship models were designed for irreversible and reversible acetylcholinesterase inhibitors by molecular modeling methods. In case of irreversible inhibitors CoMFA (the comparative analysis of molecular fields) or CoMSIA (the comparative analysis of indexes of molecular similarity) descriptors together with HYBOT 3D fields provide more statistically valid 3D-QSAR models. This indicates importance of donor-acceptor interactions for irreversible acetylcholinesterase inhibition. In case of reversible organophosphorous inhibitors good quality model for structure-activity relationships was developed using CoMFA fields. The obtained models have good predictive power and can be used for estimation of new organophosphorous compounds inhibitor activity that in turn correlates with toxicity of these compounds.

Developmental neurotoxicity testing: A path forward

“…; Tikhonova et al. ). However, there are no well‐developed or accepted QSAR/read‐across models for DNT.…”

“…developmental toxicity, Hewitt et al 2010; acute fish toxicity, Schuurmann et al 2011). There are limited numbers of SAR/QSAR models for adult neurotoxicity, for example organophosphorus induced delayed neuropathy (Malygin et al 2003), or cholinesterase inhibition (El Yazal et al 2001;Tikhonova et al 2011). However, there are no well-developed or accepted QSAR/read-across models for DNT.…”