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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

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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… Click to show full abstract

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.

Keywords: series substituted; substituted trimethyl; inhibitory; mao inhibitory; ylthio; neuroprotective mao

Journal Title: Molecules
Year Published: 2022

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