New 2-Pyrazoline and Hydrazone Derivatives as Potent and Selective Monoamine Oxidase A Inhibitors


Salgin-Goksen U., TELLİ G., Erikci A., Dedecengiz E., TEL B. C., KAYNAK F. B., ...Daha Fazla

Journal of Medicinal Chemistry, cilt.64, sa.4, ss.1989-2009, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 64 Sayı: 4
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1021/acs.jmedchem.0c01504
  • Dergi Adı: Journal of Medicinal 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
  • Sayfa Sayıları: ss.1989-2009
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

© 2021 American Chemical Society.Thirty compounds having 1-[2-(5-substituted-2-benzoxazolinone-3-yl) acetyl]-3,5-disubstitutedphenyl-2-pyrazoline structure and nine compounds having N′-(1,3-disubstitutedphenylallylidene)-2-(5-substituted-2-benzoxazolinone-3-yl)acetohydrazide skeleton were synthesized and evaluated as monoamine oxidase (MAO) inhibitors. All of the compounds exhibited selective MAO-A inhibitor activity in the nanomolar or low micromolar range. The results of the molecular docking for hydrazone derivatives supported the in vitro results. Five compounds, 6 (0.008 μM, Selectivity Index (SI): 9.70 × 10-4), 7 (0.009 μM, SI: 4.55 × 10-5), 14 (0.001 μM, SI: 8.00 × 10-4), 21 (0.009 μM, SI: 1.37 × 10-5), and 42 (0.010 μM, SI: 5.40 × 10-6), exhibiting the highest inhibition and selectivity toward hMAO-A and nontoxic to hepatocytes were assessed for antidepressant activity as acute and subchronic in mice. All of these five compounds showed significant antidepressant activity with subchronic administration consistent with the increase in the brain serotonin levels and the compounds crossed the blood-brain barrier according to parallel artificial membrane permeation assay. Compounds 14, 21, and 42 exhibited an ex vivo MAO-A profile, which is highly consistent with the in vitro data.