Biological activity evaluation of novel monoamine oxidase inhibitory compounds targeting Parkinson disease

Dawbaa S., EVREN A. E., SAĞLIK B. N., GÜNDOĞDU KARABURUN N., KARABURUN A. Ç.

Future medicinal chemistry, cilt.14, sa.22, ss.1663-1679, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 22
  • Basım Tarihi: 2022
  • Doi Numarası: 10.4155/fmc-2022-0167
  • Dergi Adı: Future medicinal chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1663-1679
  • Anahtar Kelimeler: benzofuran, carbohydrazide, molecular docking, molecular dynamics simulation, monoamine oxidase inhibitors, oxadiazol, Parkinson disease
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Evet

Özet

Aim: Design of 5-methoxy benzofuran hybrids with 2-carbohydrazide and 2-(1,3,4-oxadiazol-2-yl) as potential inhibitors of monoamine oxidase (MAO)-B targeting Parkinson disease. Materials and methods: 12 compounds were synthesized and analyzed via high-resolution mass spectrometry, 1H nuclear magnetic resonance and 13C nuclear magnetic resonance techniques. In vitro fluorometric assay was used to investigate the activity of the synthesized compounds on both MAO-A and MAO-B isozymes. Results: Three compounds - 3a, 3c and 3e - displayed half maximal inhibitory concentration values of 0.051 ± 0.002, 0.038 ± 0.001 and 0.077 ± 0.003 μM in the inhibition of MAO-A and 0.048 ± 0.002, 0.040 ± 0.001 and 0.072 ± 0.002 μM for MAO-B, respectively. A molecular dynamics simulation study showed that compound 3c has poor stability as a complex with MAO-A. Conclusion: Compound 3c may be a potential candidate for the treatment of Parkinson disease.