Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 103, Issue -, Pages 583-593Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2015.09.021
Keywords
Isatin; Pyrazole; Sulfonamide; Carbonic anhydrase inhibitor; Molecular docking
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Funding
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
- department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo, Egypt
- Deanship of Scientific Research at King Saud University [PRG-1436-05]
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New series of benzenesulfonamide derivatives incorporating pyrazole and isatin moieties were prepared using celecoxib as lead molecule. Biological evaluation of the target compounds was performed against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) and more precisely against the human isoforms hCA I, II (cytosolic), IX and XII (transmembrane, tumor-associated enzymes). Most of the tested compounds efficiently inhibited hCA I, II and IX, with K(1)s of 2.5-102 nM, being more effective than the reference drug acetazolamide. Compounds 11e, 11f, 16e and 16f were found to inhibit hCA XII with Ki of 3.7, 6.5, 5.4 and 7.2 nM, respectively. Compounds lie and 16e, with 5-NO2 substitution on the isatin ring, were found to be selective inhibitors of hCA IX and hCA XII. Docking studies revealed that the NO2 group of both compounds participate in interactions with Asp132 within the hCA IX active site, and with residues Lys67 and Asp130 in hCA XII, respectively. (C) 2015 Elsevier Masson SAS. All rights reserved.
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