Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I and II, and extracellular isoforms IV, IX, and XII with sulfamides incorporating sugar moieties.
A series of glycosylated sulfamides possessing a diverse substitution pattern, with benzylated, peracetylated, and unsaturated six- and five-membered ring sugar moieties attached to the NHSO(2)NH(2) zinc binding group is reported. These derivatives were tested for the inhibition of five human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IV, IX, and XII. Against hCA I the sulfamides behaved as weak inhibitors, whereas they showed low nanomolar activity against hCA II, IX, and XII, being slightly less effective as hCA IV inhibitors. One compound showed selectivity for inhibiting the tumor-associated isoforms hCA IX and XII over the ubiquitous cytosolic hCA II. The sulfamide zinc binding group may thus indeed lead to very effective glycosylated inhibitors targeting several physiologically relevant isozymes.
Colinas
Pedro A
PA
LADECOR, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115, 1900 La Plata, Argentina.
Bravo
Rodolfo D
RD
Vullo
Daniela
D
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000577:Amides / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000737:chemistry
D000577:Amides; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes