Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Khloya, Poonam; Ceruso, Mariangela; Ram, Sita; Supuran, Claudiu T.; Sharma, Pawan K.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3208
• Page End: 3212
• Publication Date: 2015-08-15
• Subjects: Pyrazoles -- Carbonic anhydrase isoforms I, II, IX, XII -- Acetazolamide; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.096
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of pyrazolylpyrazolines was designed, synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against cytosolic human (h) isozymes hCA I and hCA II as well as transmembrane tumor associated isozymes, hCA IX and hCA XII. All the tested compounds exhibited an excellent CA activity profile against hCA I, hCA II and hCA XII when compared to the reference drug acetazolamide (AZA). Compounds6d, 6f and7a –7f have exhibited better inhibition profile against hCA XII ( K i = 0.47–5.1 nM) as compared with AZA ( K i = 5.7 nM) especially, compounds6a, 7a, 7c and7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds6c, 6d, 7c and7d ( K i = 1.1–1.7 nM) were many fold better inhibitors than AZA ( K i = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.