Design, Synthesis and Evaluation of 8-Thiosubstituted 1,3,7- Trimethylxanthine Hydrazones with In-vitro Neuroprotective and MAO-B Inhibitory Activities-Reference-Cited by-同舟云学术

Design, Synthesis and Evaluation of 8-Thiosubstituted 1,3,7- Trimethylxanthine Hydrazones with In-vitro Neuroprotective and MAO-B Inhibitory Activities

Published:2020-04-17 Issue:3 Volume:16 Page:326-339
ISSN:1573-4064
Container-title:Medicinal Chemistry
language:en
Short-container-title:MC

Author:

Mitkov Javor¹,Kasabova-Angelova Alexandra²,Kondeva-Burdina Magdalena²,Tzankova Virginia²,Tzankova Diana¹,Georgieva Maya¹,Zlatkov Alexander¹

Affiliation:

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

2. 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

Abstract

Objective:The syntheses and biological activities of 8-thiosubstituted-1,3,7- trimethylxanthine derivatives bearing an aromatic hydrazide-hydrazone fragment in the side chain at C8 are described.Methods:The chemical structures of the synthesized compounds 6a-m were confirmed based on their MS, FTIR, 1H NMR and 13C NMR analyses.Results:The in vitro investigations of neuroprotective effects manifested on cellular (human neuroblastoma cell line SH-SY5Y) and sub-cellular (isolated rat brain synaptosomes) levels show that compounds 6g and 6i demonstrate statistically significant activity. The performed monoamine oxidase B (MAO-B) inhibition study in vitro show that compounds 6g and 6i possess a significant MAO-B inhibition activity close to L-deprenyl.Conclusion:These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for the treatment of Parkinson’s disease.

Publisher

Bentham Science Publishers Ltd.

Subject

Drug Discovery

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