# Ligand and structure-based toxicological assessment of (thio)semicarbazones on cholinesterases

## TL;DR

This study assesses the neurotoxic potential of six thiosemicarbazone compounds using computational methods and finds that some may inhibit cholinesterases and harm aquatic life.

## Contribution

The study introduces a structure–toxicity relationship for thiosemicarbazones using ligand- and structure-based computational approaches.

## Key findings

- Bromine substitution increases electrophilicity, while sulfur and nitrogen are key nucleophilic sites in TSCBZ.
- TSCBZ1, 4, and 6 may cause acute and chronic toxicity in aquatic organisms.
- TSCBZ1 and TSCBZ4 show higher acetylcholinesterase affinity than galantamine, indicating potential selective inhibition.

## Abstract

Thiosemicarbazones (TSCBZ) are promising insecticidal compounds, but their potential neurotoxicity remains unclear. This study aimed to evaluate the toxicity and cholinesterase inhibition of six substituted TSCBZ derivatives using ligand- and structure-based computational approaches. Electronic property analysis revealed that bromine substitution enhances electrophilicity, while sulfur (in TSCBZ1–3) and nitrogen (in TSCBZ4–6) are the most nucleophilic sites. Toxicity prediction indicated that TSCBZ1, 4, and 6 may induce acute and chronic effects in aquatic organisms. Molecular docking showed that TSCBZ1 and TSCBZ4 exhibit higher affinity for acetylcholinesterase than galantamine, suggesting potential selective inhibition. These findings provide novel insights into the structure–toxicity relationship of TSCBZ and their environmental safety profile.

The online version contains supplementary material available at 10.1007/s10822-025-00746-6.