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

Journal of Computer-Aided Molecular Design 2026 Open access

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Authors: Damião Sampaio de Sousa, Akenaton Onassis Cardoso Viana Gomes, Caio Henrique Alexandre Roberto, Anthony Barbosa Belarmino, Francisco Rogênio da Silva Mendes, Márcia Machado Marinho, Pedro de Lima‐Neto, Gabrielle Silva Marinho
DOI: 10.1007/s10822-025-00746-6
Cited by: 4
References: 101

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.

Fields of Study & Subjects

Cholinesterase and Neurodegenerative Diseases Pesticide Exposure and Toxicity Environmental Toxicology and Ecotoxicology

Publication details

Journal / source
Journal of Computer-Aided Molecular Design
Publisher
Springer Science and Business Media LLC
Volume
40
Issue
1
Pages
40–40
Publication date
8 January 2026
Language
EN