Novel 2,5-disubstituted-1,3,4-oxadiazole derivatives as MAO-B inhibitors: Synthesis, biological evaluation and molecular modeling studies

TOK F., Ugras Z., SAĞLIK B. N., ÖZKAY Y., KAPLANCIKLI Z. A., KAYMAKÇIOĞLU B.

BIOORGANIC CHEMISTRY, cilt.112, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 112
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.bioorg.2021.104917
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: MAO inhibitors, 1, 3, 4-oxadiazole, Molecular docking, Urea derivatives, IN-SILICO EVALUATION, DESIGN, VITRO, 1,3,4-OXADIAZOLE, COMPLEXES, HYDRAZONE, DOCKING, MOIETY
  • Marmara Üniversitesi Adresli: Evet

Özet

Thirty novel 2,5-disubstituted-1,3,4-oxadiazole derivatives bearing urea moiety were designed and synthesized. IR, 1H-NMR, 13C-NMR and mass spectroscopic methods and elemental analysis were used to confirm the structures of the compounds. Their monoamine oxidase inhibitory activity was determined against the MAO-A and MAO-B isoforms. None of the compounds showed the potent MAO-A inhibitory activity, while the MAO-B inhibition was significantly found in the range of 62 to 98%. Among them, the compounds H8, H9 and H12 bearing chloro substituent at the fourth position of phenylurea were found to show potent monoamine oxidase B inhibitory activity with IC50 values 0.039-0.066 mu M. To define and evaluate the interaction mechanism between compound H8 and monoamine oxidase B, molecular docking studies have been made.