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). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.
Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII / Khloya, Poonam; Ceruso, Mariangela; Ram, Sita; Supuran, Claudiu T.; Sharma, Pawan K.. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - STAMPA. - 25:(2015), pp. 3208-3212. [10.1016/j.bmcl.2015.05.096]
Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms I, II, IX and XII
CERUSO, MARIANGELA;SUPURAN, CLAUDIU TRANDAFIR;
2015
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). Compounds 6d, 6f and 7a-7f have exhibited better inhibition profile against hCA XII (Ki = 0.47-5.1 nM) as compared with AZA (Ki = 5.7 nM) especially, compounds 6a, 7a, 7c and 7d which were nearly 10-fold better than reference drug. Against hCA II, all of the tested compounds were better than the standard drug especially compounds 6c, 6d, 7c and 7d (Ki = 1.1-1.7 nM) were many fold better inhibitors than AZA (Ki = 12.1 nM). In addition, they acted as selective CA inhibitors of isoform hCA XII over the physiological isoform hCA I.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.