Design, synthesis and evaluation of semi- and thiosemicarbazides containing a methylxanthine moiety with in vitro neuroprotective and MAO-B inhibitory activities

Abstract

AbstractThis study is focused on determination of the most appropriate synthetic approach for obtaining series of theophylline-7-acetyl semi- and thiosemicarbazide hybrids by using the molecular hybridization strategy with and without a catalyst. The target derivatives were further investigated for their in vitro neurotoxic and neuroprotective effects on cellular and subcellular level, along with their possible MAO-B inhibitory activities. The results identified 2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)-N-[(methylcarbamo-thioyl)amino] acetamide (5) as the most promising structure for further in vivo evaluations with the lowest neurotoxicity and the highest neuroprotection and MAO B inhibitory activity of 28%.

Keywords

• xanthines
• monoamine oxidase B inhibition
• neurotoxicity
• neuroprotection