Quantitative Structure–Neurotoxicity Assessment and In Vitro Evaluation of Neuroprotective and MAO-B Inhibitory Activities of Series <i>N</i>′-substituted 3-(1,3,7-trimethyl-xanthin-8-ylthio)propanehydrazides
Magdalena Kondeva-Burdina,
Javor Mitkov,
Iva Valkova,
Lily Peikova,
Maya Georgieva,
Alexander Zlatkov
Affiliations
Magdalena Kondeva-Burdina
Laboratory of Drug Metabolism and Drug Toxicity, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
Javor Mitkov
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
Iva Valkova
Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
Lily Peikova
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
Maya Georgieva
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
Alexander Zlatkov
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria
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.
