Design, Synthesis and Anxiolytic Activity Evaluation of N-Acyltryptophanyl-Containing Dipeptides, Potential TSPO Ligands

The study designed and synthesized N-acyltryptophanyl-containing dipeptides as potential ligands for the TSPO, which is linked to neurosteroid biosynthesis and anxiolytic effects. The lead compound, GD-23, showed significant anxiolytic activity in vivo, comparable to diazepam, at doses of 0.05 to 5.0 mg/kg. The anxiolytic mechanism was confirmed to involve the TSPO receptor, as demonstrated by antagonism with the TSPO selective inhibitor PK11195 and inhibitors of neurosteroid biosynthesis enzymes. The research suggested that N-acyl-L-tryptophanyl-isoleucine amides could be a novel class of TSPO ligands with potential anxiolytic properties.