Computational investigation of behavioral toxicity syndromes (BTS) of synthetics halosubstituted semicarbazones.

Semicarbazones have been used as insecticides and act through different mechanisms of action by inhibiting enzymes essential for insect metabolism, including enzymes that act on the central nervous system of insects associated with other general toxic effects for these organisms. In this context, the purpose of the study was to evaluate the toxicity of semicarbazones and their respective substituent groups using in silico toxicological modeling approach, analyzing the stability between ligand-receptor and their structure/activity relationship (SAR) to establish relationships between behavioral toxicity syndrome (BTS) in fish as a method of environmental biomonitoring. Quantum calculations were obtained using the Density Functional Theory method for electronic structural characterization. Toxicity prediction was carried out using the Ecological Structure Activity Relationship (ECOSAR) predictive model, which estimates the acute and chronic toxicity of organic compounds in aquatic organisms such as fish, aquatic invertebrates, and aquatic plants. Molecular docking simulations were conducted using the Autodock Vina software against the target acetylcholinesterase (AChE). The protein-ligand complexes with the lowest energy and RMSD of less than 2 Å were submitted to molecular dynamics simulations. The quantum data corroborates the surface analysis of lipophilicity, which indicates that the alkenyl substituent chain has a greater partition contribution fragment in which dihalogenated derivatives increase in this proportion. The HOMO-LUMO gap (∆ Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00437-y.