In vitro and in silico investigation of inhibitory activities of 3-arylcoumarins and 3-phenylazo-4-hydroxycoumarin on MAO isoenzymes

Yuce-Dursun B., Danış Ö., Ozalp L., Sahin E., Demir S., Erdem S., ...Daha Fazla

STRUCTURAL CHEMISTRY, cilt.34, sa.5, ss.1715-1729, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 34 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s11224-022-02092-x
  • Dergi Adı: STRUCTURAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, INSPEC
  • Sayfa Sayıları: ss.1715-1729
  • Anahtar Kelimeler: Enzyme inhibition, Coumarin, Drug design, Monoamine oxidase a/b, Molecular docking, Molecular dynamics, MONOAMINE-OXIDASE-B, VALENCE-BOND SIMULATIONS, HYDRIDE-TRANSFER STEP, COUMARIN DERIVATIVES, 2H-CHROMEN-2-ONE DERIVATIVES, CATALYZED METABOLISM, ANTIOXIDANT ACTIVITY, OXIDATION MECHANISM, MOLECULAR-DYNAMICS, DUAL INHIBITORS
  • Marmara Üniversitesi Adresli: Evet

Özet

A series of 3-aryl coumarin derivatives and 3-phenylazo-4-hydroxycoumarin were evaluated for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity by fluorometric enzymological assays. Among 21 coumarin derivatives, compound 21 (3-phenylazo-4-hydroxycoumarin) displayed a good inhibitory activity (0.12 +/- 0.02 mu M) and very high selectivity for MAO-B (SI > 833.33). The inhibition was determined as mixed-type and not time-dependent. Docking studies, molecular dynamics and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculations were performed to elucidate in vitro results. Our results reveal that the insertion of an azo linker between coumarin and phenyl rings in 3-arylcoumarins enhances MAO-B selectivity enormously since such a linker leads to the perfect alignment of the coumarin ring in the aromatic cage and the phenyl ring in the entrance cavity of MAO-B active site. Hydrogen bond interactions with Cys172 in the active site entrance of MAO-B also contributes to the remarkably higher inhibitory activity and selectivity for MAO-B.