Salithion

Salithion is an acetylcholinesterase inhibitor and neurotoxicant. Salithion binds to the active site of acetylcholinesterase to interfere with acetylcholine hydrolysis, and there is an enantioselective difference between its (R) and (S) enantiomers^[1]. In Vitro:(S)-dioxabenzofos (1.0-144 μM; 24 h) more potently inhibits intracellular AChE activity in SH-SY5Y human neuroblastoma cells than (R)-dioxabenzofos (1.0-144 μM; 24 h), with IC₅₀ values of 5.28 μM and 17.2 μM, respectively, after 24 h of exposure^[1].
(S)-dioxabenzofos (2.5-22.5 μM) exhibits higher bioaffinity for purified AChE than (R)-dioxabenzofos (2.5-22.5 μM), with Stern-Volmer constants of 5.691×10⁴ M^-1 and 1.947×10⁴ M^-1, respectively, and causes greater quenching of AChE intrinsic Trp fluorescence^[1].
(S)-dioxabenzofos forms more stable and numerous noncovalent bonds, including stronger hydrogen bonds, with key active-site residues of AChE than (R)-dioxabenzofos, resulting in a higher calculated bioaffinity (5.012×10⁴ M^-1 vs. 1.905×10⁴ M^-1)^[1].
(S)-dioxabenzofos (200,000 ps) forms more stable, high-affinity complexes with AChE than (R)-dioxabenzofos (200,000 ps) during dynamic simulation, with a lower (more favorable) average binding free energy of -23.55 kcal mol⁻¹ compared to -15.43 kcal mol⁻¹ for (R)-dioxabenzofos^[1].