Design, Synthesis and Biological Evaluation of Potent Antioxidant 1-(2,5-Dimethoxybenzyl)-4-arylpiperazines and N-Azolyl Substituted 2-(4-Arylpiperazin-1-yl)


Saadeh H. A., Khasawneh M. A., Samadi A., ELHATY I. A. M., Satała G., Bojarski A. J., ...Daha Fazla

ChemistrySelect, cilt.2, sa.13, ss.3854-3859, 2017 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 2 Sayı: 13
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1002/slct.201700397
  • Dergi Adı: ChemistrySelect
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.3854-3859
  • Anahtar Kelimeler: Antioxidants, N-azolyl substituted 2-(4-arylpiperazin-1-yl), coupled G-receptors, 1-(2,5-dimethoxybenzyl)-4-arylpiperazines, MAO/5-HT6 modulators
  • İstanbul Gelişim Üniversitesi Adresli: Hayır

Özet

We describe here the synthesis, antioxidant capacity, and biological activities on MAO, ChE, and selected GPCRs, of novel 1-(2,5-dimethoxybenzyl)-4-arylpiperazines 1–10, as well as known N-(2-(2-methyl-5-nitro-1H-imidazol-1-yl))-2-(4-arylpiperazin-1-yl) 11–20 and N-(5-nitrothiazol-2-yl)-2-(4-arylpiperazin-1-yl) 21–29. Some of the new 4-arylpiperazines were found to have low-micromolar affinities for the proteins tested. The most potent MAO inhibitor identified was compound 2-(4-(3-fluorophenyl)-yl)-N-(5-nitrothiazol-2-yl)(27), with an IC50 value of 4.14 ± 0.5 μM, whereas the most potent interaction with a GPCR was 1-(2,5-dimethoxybenzyl)-4-(4-trifluoromethylphenyl) (5) for the 5-HT6 serotonin receptor, with a Ki value of 0.7 μM. Interestingly, some of the compounds described here showed impressive antioxidant potential. Of mention, compounds 1, 6, 7, and 23 had trolox/equivalent ORAC values of 9.10, 8.80, 8.82, and 9.42, respectively, all of them being significantly higher than the TE determined for ferulic acid (3.74), a standard antioxidant. Among all molecules synthesized and tested, compound 23 can be regarded as an interesting low-micromolar MAO−B/5-HT6 dual inhibitor lead with potent antioxidant properties.