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Evaluation of selective human MAO inhibitory activities of some novel pyrazoline derivatives

  • Translational Neurosciences - Original Article
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Abstract

A series of 1-[2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetyl]-3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives were prepared by reacting 2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetylhydrazine with appropriate chalcones. The chemical structures of all compounds were confirmed by elemental analyses, IR, 1H NMR and ESI–MS. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in vitro tests. MAO activities of the compounds were compared with moclobemide and selegiline and all the compounds were found to inhibit human MAO-A selectively. The inhibition profile was found to be competitive and reversible for all compounds by in vitro tests. Among the compounds examined, compounds 5ae, 5af and 5ag were more selective than moclobemide, with respect to the K i values experimentally found. In addition, the compound 5bg showed MAO-A inhibitor activity as well as moclobemide. A series of experimentally tested compounds (5ae–5ch) were docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The AUTODOCK 4.01 program was employed to perform automated molecular docking.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100 Sıhhıye, Ankara, Turkey

    Umut Salgın-Gökşen & Nesrin Gökhan-Kelekçi

  2. Turkish Medicines and Medical Devices Agency, Analyses and Control Laboratories, 06100, Ankara, Turkey

    Umut Salgın-Gökşen

  3. Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, 06100, Sıhhıye, Ankara, Turkey

    Samiye Yabanoğlu-Çiftçi, Ayşe Ercan & Gülberk Uçar

  4. Bioinformatics and Genetics Deparment, Faculty of Engineering and Natural Sciences, Kadir Has University, 34083, Fatih, Istanbul, Turkey

    Kemal Yelekçi

Authors
  1. Umut Salgın-Gökşen
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  2. Samiye Yabanoğlu-Çiftçi
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  3. Ayşe Ercan
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  4. Kemal Yelekçi
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  5. Gülberk Uçar
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  6. Nesrin Gökhan-Kelekçi
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Correspondence to Gülberk Uçar.

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Salgın-Gökşen, U., Yabanoğlu-Çiftçi, S., Ercan, A. et al. Evaluation of selective human MAO inhibitory activities of some novel pyrazoline derivatives. J Neural Transm 120, 863–873 (2013). https://doi.org/10.1007/s00702-013-0980-6

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  • DOI: https://doi.org/10.1007/s00702-013-0980-6

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