Publication: In vitro and in silico investigation of inhibitory activities of 3-arylcoumarins and 3-phenylazo-4-hydroxycoumarin on MAO isoenzymes
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Date
2022-11-01
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Abstract
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.
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Kimya, Biyokimya, Alkoloidler, Fizikokimya, Sıvı Kristaller ve Sıvı Kristal Polimerler, Temel Bilimler, Chemistry, Biochemistry, Alcaloides, Physical Chemistry, Liquid Crystals and LCP, Natural Sciences, KİMYA, MULTİDİSİPLİNER, Temel Bilimler (SCI), KİMYA, FİZİKSEL, KRİSTALLOGRAFİ, CHEMISTRY, MULTIDISCIPLINARY, CHEMISTRY, Natural Sciences (SCI), CHEMISTRY, PHYSICAL, CRYSTALLOGRAPHY, Yüzeyler ve Arayüzler, Yüzeyler, Kaplamalar ve Filmler, Fiziksel ve Teorik Kimya, Kimya (çeşitli), Genel Kimya, Fizik Bilimleri, Surfaces and Interfaces, Surfaces, Coatings and Films, Physical and Theoretical Chemistry, Chemistry (miscellaneous), General Chemistry, Physical Sciences, 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, Enzyme inhibition · Coumarin · Drug design · Monoamine oxidase a/b · Molecular docking · Molecular dynamics
Citation
Yuce-Dursun B., DANIŞ Ö., Ozalp L., Sahin E., DEMİR S., ERDEM S., OGAN A., "In vitro and in silico investigation of inhibitory activities of 3-arylcoumarins and 3-phenylazo-4-hydroxycoumarin on MAO isoenzymes", STRUCTURAL CHEMISTRY, 2022