2. Academic Validation
  3. Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

Synthesis of New Hydrazone Derivatives for MAO Enzymes Inhibitory Activity

  • Molecules. 2017 Aug 20;22(8):1381. doi: 10.3390/molecules22081381.
Nafiz Öncü Can 1 2,  Derya Osmaniye 3 4,  Serkan Levent 5 6,  Begüm Nurpelin Sağlık 7 8,  Beril İnci 9,  Sinem Ilgın 10,  Yusuf Özkay 11 12,  Zafer Asım Kaplancıklı 13
Affiliations

Affiliations

  • 1 Department of Analytical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. nafizoc@anadolu.edu.tr.
  • 2 Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. nafizoc@anadolu.edu.tr.
  • 3 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. dosmaniye@anadolu.edu.tr.
  • 4 Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. dosmaniye@anadolu.edu.tr.
  • 5 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. serkanlevent@anadolu.edu.tr.
  • 6 Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. serkanlevent@anadolu.edu.tr.
  • 7 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. bnsaglik@anadolu.edu.tr.
  • 8 Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. bnsaglik@anadolu.edu.tr.
  • 9 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. inci57@anadolu.edu.tr.
  • 10 Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. silgin@anadolu.edu.tr.
  • 11 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. yozkay@anadolu.edu.tr.
  • 12 Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. yozkay@anadolu.edu.tr.
  • 13 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu Universty, 26470 Eskişehir, Turkey. zakaplan@anadolu.edu.tr.
PMID: 28825649 DOI: 10.3390/molecules22081381
Abstract

In the present work, 14 new 1-substituted-2-phenylhydrazone derivatives were synthesized to evaluate their inhibitory activity against hMAO Enzymes. The structures of the newly synthesized hydrazones 2a-2n were characterized by IR, 1H-NMR, 13C-NMR, HR-MS spectroscopic methods. The inhibitory activity of compounds 2a-2n against hMAO-A and hMAO-B Enzymes was elucidated by using an in-vitro Amplex Red® reagent assay based on fluorometric methods. According to the activity studies, 2a and 2b were found to be the most active compounds against hMAO-A Enzyme, with IC50 values of 0.342 µM and 0.028 µM, respectively. The most active compounds 2a-2b were evaluated by means of Enzyme kinetics and docking studies. Moreover, these compounds were subjected to cytotoxicity and genotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic and non-genotoxic. Consequently, the findings of this study display the biological importance of compounds 2a, 2b as selective, irreversible and competitive inhibitors of hMAO-A. Docking studies revealed that there is a strong interaction between hMAO-A and the most active compound 2b.

Keywords

hydrazone, MAO enzymes inhibition, docking studies, genotoxicity, cytotoxicity.

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