Application of the hard and soft, acids and bases (HSAB) theory as a method to predict cumulative neurotoxicity.

ABSTRACT: Xenobiotic electrophiles can form covalent adducts that may impair protein function, damage DNA, and may lead a range of adverse effects. Cumulative neurotoxicity is one adverse effect that has been linked to covalent protein binding as a Molecular Initiating Event (MIE). This paper describes a mechanistic in silico chemical screening approach for neurotoxicity based on Hard and Soft Acids and Bases (HSAB) theory. We evaluated the applicability of HSAB-based electrophilicity screening protocol for neurotoxicity on 19 positive and 19 negative reference chemicals. These reference chemicals were identified from the literature, using available information on mechanisms of neurotoxicity whenever possible. In silico screening was based on structural alerts for protein binding motifs and electrop

SUBMITTER: Melnikov F 

PROVIDER: S-EPMC7369154 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature