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

[ Vol. 16 , Issue. 3 ]

Author(s):

Javor Mitkov, Alexandra Kasabova-Angelova, Magdalena Kondeva-Burdina, Virginia Tzankova, Diana Tzankova, Maya Georgieva and Alexander Zlatkov*   Pages 326 - 339 ( 14 )

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.

Keywords:

Alzheimer's disease, xanthine, aromatic hydrazide-hydrazones, SH-SY5Y, monoamine oxidase B, Parkinson’s disease.

Affiliation:

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

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