Endogenous and Phytochemical Acyl-Tryptamine Conjugates Six Structural Classes of Novel Multi-Target Prodrug Candidates for Neuroinflammation, Metal Dysregulation, and Serotonergic Modulation

This preprint presents eighteen novel N-acyl tryptamine conjugates organised into six structural classes — indoloyl, thiazolyl, imidazolyl, feruloyl, coumaroyl, and salicyloyl — as hypothetical multi-target prodrug candidates for neurological and neuroinflammatory conditions. All compounds share a secondary amide bond linking a bioactive acyl moiety to substituted tryptamine scaffolds (4-hydroxy, 5-methoxy, or 4-acetoxy), with enzymatic hydrolysis proposed to simultaneously release a serotonergic tryptamine and a pharmacologically active acyl fragment. The six acyl classes introduce mechanistically distinct secondary hypotheses: aryl hydrocarbon receptor (AhR) activation, endogenous Zn²⁺/Cu²⁺ chelation, NF-κB inhibition, MAO-B inhibition, enhanced CNS penetration, and serotonergic–COX dual activity. All eighteen compounds are new chemical entities. No synthesis or biological testing has been performed. SMILES strings and predicted physicochemical properties (Lipinski's Rule of Five, cLogP, TPSA) are provided to facilitate computational docking, QSAR modelling, and synthetic planning.