Study on the toxicity prediction model ofacetolactate synthase inhibitor herbicides based on human serum albumin and superoxide dismutase binding information

Abstract

Toxicity significantly influences the successful development of drugs. Based on the toxicity prediction method (carrier protein binding information-toxicity relationship) previously established by the our group, this paper introduces information on the interaction between pesticides and environmental markers (SOD) into the model for the first time, so that the toxicity prediction model can not only predict the toxicity of pesticides to humans and animals, but also predict the toxicity of pesticides to the environment. Firstly, the interaction of acetolactate synthase inhibitor herbicides (ALS inhibitor herbicides) with human serum albumin (HSA) and superoxide dismutase (SOD) was investigated systematically from theory combined with experiments by spectroscopy methods and molecular docking, and important fluorescence parameters were obtained. Then, the fluorescence parameters, pesticides acute toxicity LD₅₀ and structural splitting information were used to construct predictive modeling of ALS inhibitor herbicides based on the carrier protein binding information (R² = 0.977) and the predictive modeling of drug acute toxicity based on carrier protein binding information and conformational relationship (R² = 0.991), which had effectively predicted pesticides toxicity in humans and animals. To predict potential environmental toxicity, the predictive modeling of drug acute toxicity based on superoxide dismutase binding information was established (R² = 0.883) by ALS inhibitor herbicides-SOD binding information, which has a good predictive ability in the potential toxicity of pesticides to the environment. This study lays the foundation for developing low toxicity pesticides.

Keywords: Human serum albumin; Superoxide dismutase; Toxicity prediction.