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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

Author(s):

Javor Mitkov, Alexandra Kasabova-Angelova, Magdalena Kondeva-Burdina, Virginia Tzankova, Diana Tzankova, Maya Georgieva and Alexander Zlatkova*   Pages 1 - 14 ( 14 )

Abstract:


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. The chemical structures of the synthesized compounds 6a-m were confirmed based on their MS, FTIR, 1H NMR and 13C NMR analyses. 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. 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:

Xanthine; aromatic hydrazide-hydrazones, SH-SY5Y, monoamine oxidase B.

Affiliation:

Department “Pharmaceutical, Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Laboratory “Drug metabolism and drug toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Laboratory “Drug metabolism and drug toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Laboratory “Drug metabolism and drug toxicity”, Department “Pharmacology, Pharmacotherapy and Toxicology”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Department “Pharmaceutical, Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Department “Pharmaceutical, Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia, Department “Pharmaceutical, Chemistry”, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav str., 1000, Sofia



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