Carbonic anhydrase inhibitors. Part 76 - Inhibition of isozyme I, II and IV by sulfacetamide derivatives

A series of sulfacetamide derivatives has been prepared by reaction of alky l,- arylalkyl- and arylsulfonyl halides or sulfonic acid anhydrides with th e title sulfonamide. Other compounds have been obtained from sulfenyl chlor ides, acyl chlorides, or tosyl isocyanate and sulfacetamide. Inhibition of three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human ; b = bovine) with the prepared compounds has been investigated. Good inhib itors, as well as compounds with moderate activity against these isozymes w ere detected depending on the nature of the R group substituting the N-4 at om in these new sulfacetamide derivatives. Compounds of the types RSNH-C6H4 -SO2NHAc and RCONH-C6H4-SO2NHAc were less active in inhibiting all the inve stigated isozymes as compared to the stronger inhibitors possessing the gen eral formula RSO2NH-C6H4-SO2NHAc. Susceptibility to inhibition with the sul facetamide derivatives was generally: hCA II > bCA IV > hCA I. Spectroscopi c studies on Co(II)-substituted hCA II proved that the new inhibitors direc tly bind to the metal ion within the enzyme active site, similarly to the c lassical inhibitors of the unsubstituted sulfonamide type.