Quantitative Structure–Neurotoxicity Assessment and In Vitro Evaluation of Neuroprotective and MAO-B Inhibitory Activities of Series N′-substituted 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazides

The neurotoxic, neuroprotective and MAO-B inhibitory effects of series N′-substituted 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazides are evaluated. The results indicate compounds N′-(2,3-dimethoxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6k) and N′-(2-hydroxybenzylidene)-3-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylthio)propanehydrazide (6l) as most perspective. The performed QSTR analysis identified that the decreased lipophilicity and smaller dipole moments of the molecules are the structural features ensuring lower neurotoxicity. The obtained results may be used as initial information in the further design of (xanthinyl-8-ylthio)propanhydrazides with potential hMAOB inhibitory effect and pronounced neuroprotection.