Computational ecotoxicological assessment and molecular modeling of sophalines from Sophora alopecuroides with insights into potential GABAergic-like sedative

Abstract Sophalines isolated from Sophora alopecuroides have been recognized for their antiviral properties; however, their potential neurotoxic and ecotoxicological effects remain poorly understood. In this study, the toxicity and putative GABAergic-like activity of these compounds were investigated using computational approaches. Model-based ecotoxicological estimations suggested that sophalines may present moderate to high toxicity toward Daphnia magna and may be associated with inhibition of biomass growth in green algae. These findings are consistent with a narcotic-like mode of action, which may be related to reduced locomotor activity and central nervous system (CNS)-associated effects, as inferred from physicochemical descriptors and CNS multiparameter optimization (CNS MPO) profiles. Comparative analysis with the reference compound diazepam indicated overlapping concentration ranges, suggesting a possible similarity in their predicted toxicological profiles. Molecular docking results suggested that sophaline derivatives may interact with the GABAAR, with some compounds occupying regions overlapping the diazepam binding site, while others were positioned in adjacent regions, indicating potential modulatory interactions. These interactions were characterized by hydrophobic contacts, hydrogen bonding, and π-interactions, which may contribute to complex stability. Molecular dynamics simulations supported the structural stability of the ligand–receptor complexes, with the D2/GABAA receptor system presenting the most favorable interaction profile among the evaluated compounds. Overall, these findings provide computational insights into the potential GABAergic-like sedative effects of sophalines. However, as all results are derived from in silico approaches, they should be interpreted as predictive rather than confirmatory. Experimental validation through in vitro and in vivo studies is required to substantiate these observations and to better assess their ecological and pharmacological relevance.