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Design, Synthesis and Biological Evaluation of Potent Antioxidant 1‐(2,5‐Dimethoxybenzyl)‐4‐arylpiperazines and N ‐Azolyl Substituted 2‐(4‐Arylpiperazin‐1‐yl)
Author(s) -
Saadeh Haythem A.,
Khasawneh Mohammad A.,
Samadi Abdelouahid,
ElHaty Ismail A.,
Satała Grzegorz,
Bojarski Andrzej J.,
Ismaili Lhassane,
BautistaAguilera Óscar M.,
Yañez Matilde,
Mestres Jordi,
MarcoContelles José
Publication year - 2017
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201700397
Subject(s) - trolox , antioxidant , chemistry , stereochemistry , antioxidant capacity , biochemistry
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‐1 H ‐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 IC 50 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‐HT 6 serotonin receptor, with a K i 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‐HT 6 dual inhibitor lead with potent antioxidant properties.