Synthesis and carbonic anhydrase inhibitory properties of novel 4-(2-aminoethyl)benzenesulfonamide-dipeptide conjugates
[Display omitted] •Benzotriazole mediated dipeptide synthesis.•Thirty new dipeptide-primary sulfonamide conjugates.•4-(2-Aminoethyl)benzenesulfonamide-dipeptide Conjugates.•Potent carbonic anhydrase (hCA I, II, IV and XII) inhibitors. Thirty novel sulfonamide derivatives incorporating dipeptide were...
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Veröffentlicht in: | Bioorganic chemistry 2019-03, Vol.83, p.414-423 |
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Format: | Artikel |
Sprache: | eng |
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•Benzotriazole mediated dipeptide synthesis.•Thirty new dipeptide-primary sulfonamide conjugates.•4-(2-Aminoethyl)benzenesulfonamide-dipeptide Conjugates.•Potent carbonic anhydrase (hCA I, II, IV and XII) inhibitors.
Thirty novel sulfonamide derivatives incorporating dipeptide were synthesized by facile acylation through benzotriazole mediated reactions and their structures were identified by 1H NMR, 13C NMR, MS and FT-IR spectroscopic techniques and elemental analysis. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV and hCA XII. Most of the synthesized compounds showed excellent in vitro carbonic anhydrase inhibitory properties comparable to those of the clinically used drug acetazolamide (AAZ). The new unprotected dipeptide-sulfonamide conjugates showed very effective inhibitory activity, in the low nanomolar range against II and XII, being less effective as hCA I and IV inhibitors. Four of the thirty compounds also showed strong inhibitory activity against hCA XII compared to AAZ. |
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ISSN: | 0045-2068 1090-2120 |
DOI: | 10.1016/j.bioorg.2018.11.003 |