Computational toxicity profiling of the UV stabilizer UV-328 against the human brain enzyme acetylcholinesterase

One of the current environmental pollutants of concern is the widespread use of the ultraviolet stabilizer UV-328, which has the potential to cause neurotoxicity. This study aimed to investigate the potential neurotoxicity of UV-328 by examining the possible interaction of UV-328 with human acetylcholinesterase through an integrated in silico methodology. The canonical active site pocket (C2) was identified as the preferred binding site, and UV-328 had a binding affinity of -8.5 kcal/mol, similar to that of tacrine and rivastigmine, and significantly weaker compared to that of the co-crystallized ligand, E20, which had a binding affinity of -12.1 kcal/mol. The stability of the UV-328-AChE complex was also observed during the 100 ns molecular dynamics simulation, as shown by the stable root mean square deviation (<0.3 nm), low fluctuations of individual residues, and invariant radius of gyration and accessible surface area. In silico predictions of ADMET and CNS penetration also indicated that UV-328 has physicochemical characteristics that are consistent with blood-brain barrier permeation. Collectively, these results suggest that a relatively stable interaction between UV-328 and acetylcholinesterase is possible, which supports the hypothesis of potential neurotoxic relevance of the compound and warrants further investigation. Reuslts are hypothetical and require experimrntal validation.