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

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.