Quantitative Structure-Activity Relationships for Organophosphate Enzyme Inhibition (Briefing Charts).

摘要

Organophosphates (OPs) are a group of pesticides that inhibit enzymes such as acetylcholinesterase. Numerous OP structural variants exist and toxicity data can be difficult to quickly obtain. To address this concern, quantitative structure-activity relationship (QSAR) models were developed to predict acetylcholinesterase, butyrycholinesterase, trypsin and chymotrypsin inhibition, key components in biologically-based dose-response (BBDR) models. The acetylcholinesterase database consisted of 747 structures developed from 69 peer reviewed publications. AMPAC and CODESSA descriptors (SemiChem, Inc.) were calculated for each compound. The acetylcholinesterase results show that the average nucleophilic reactive index for a carbon atom contributed most significantly to binding. A training R2 of 0.73-0.01 and an external test set Q2 of 0.62-0.06 was achieved. The QSAR models discussed in this seminar will complement OP BBDR modeling by filling critical data gaps for key parameter values, leading to better risk assessment and prioritization of animal and human toxicity studies especially for OPs lacking experimental data.