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

Magdalena Kondeva-Burdina; Javor Mitkov; Iva Valkova; Lily Peikova; Maya Georgieva; Alexander Zlatkov

doi:10.3390/molecules27165321

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

Molecules. 2022 Aug 20;27(16):5321. doi: 10.3390/molecules27165321.

Authors

Magdalena Kondeva-Burdina¹, Javor Mitkov², Iva Valkova³, Lily Peikova², Maya Georgieva², Alexander Zlatkov²

Affiliations

¹ 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.
² Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria.
³ Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000 Sofia, Bulgaria.

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: QSTR; monoamine oxidase B; neuroprotection; neurotoxicity; xanthine.

MeSH terms

Monoamine Oxidase Inhibitors* / chemistry
Monoamine Oxidase Inhibitors* / pharmacology
Monoamine Oxidase* / metabolism
Neuroprotection
Structure-Activity Relationship
Xanthine / chemistry

Substances

Monoamine Oxidase Inhibitors
Xanthine
Monoamine Oxidase

Grants and funding

This research received no external funding.