Title:Design, Synthesis and Evaluation of 8-Thiosubstituted 1,3,7- Trimethylxanthine Hydrazones with In-vitro Neuroprotective and MAO-B Inhibitory Activities
Volume: 16
Issue: 3
Author(s): Javor Mitkov, Alexandra Kasabova-Angelova, Magdalena Kondeva-Burdina, Virginia Tzankova, Diana Tzankova, Maya Georgieva and Alexander Zlatkov*
Affiliation:
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Street, 1000, Sofia,Bulgaria
Keywords:
Alzheimer's disease, xanthine, aromatic hydrazide-hydrazones, SH-SY5Y, monoamine oxidase B, Parkinson’s
disease.
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.