Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38 alpha MAPK (IC50= 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 mu M, respectively) compared to sorafenib (IC50= 1.58 mu M) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with K-i values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with K-i values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38 alpha MAPK/CA inhibitor.

1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38 mitogen-activated protein kinase inhibitory activity / Georgey, Hanan H; Manhi, Fatma M; Mahmoud, Walaa R; Mohamed, Nehad A; Berrino, Emanuela; Supuran, Claudiu T. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - ELETTRONICO. - 82:(2019), pp. 0-0. [10.1016/j.bioorg.2018.09.037]

1,2,4-Trisubstituted imidazolinones with dual carbonic anhydrase and p38 mitogen-activated protein kinase inhibitory activity

Berrino, Emanuela;Supuran, Claudiu T
2019

Abstract

Various 1,2,4 trisubstituted imidazolin-5-one derivatives were synthesized and evaluated for their inhibitory activity against p38 mitogen-activated protein kinase (p38MAPK) and carbonic anhydrase (CA) enzymes aiming to explore potential dual inhibitors. Results revealed that compounds 3c, 3g, 3h, 4a, 6c and 6d were the most effective derivatives against p38 alpha MAPK (IC50= 0.14, 0.14, 0.056, 0.14, 0.13 and 0.14 mu M, respectively) compared to sorafenib (IC50= 1.58 mu M) as standard drug. On the other hand, compound 4a revealed the best inhibitory activity against all the tested carbonic anhydrase isoforms CA I, II, IV and IX with K-i values of 95.0, 0.83, 6.90 and 12.4 nM, respectively compared to acetazolamide with K-i values 250, 12.1, 74 and 12.8 nM, respectively. Therefore, compound 4a can be considered as a potent dual p38 alpha MAPK/CA inhibitor.
2019
82
0
0
Georgey, Hanan H; Manhi, Fatma M; Mahmoud, Walaa R; Mohamed, Nehad A; Berrino, Emanuela; Supuran, Claudiu T
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1308099
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