Krebs (1948) reported that substitution of the sulfonamido moiety to give compounds of type ArSO2NHR drastically reduced the CA inhibitory properties compared with those of the corresponding derivatives possessing primary sulfonamido groups, ArSO2NH2. As a consequence, other zinc-binding functions except for the SO2NH2 group have rarely been considered in the design of CAIs, although many other zinc enzymes are inhibited by a multitude of derivatives possessing an entire range of zinc-binding functions, such as thiols, phosphonates, carboxylates and hydroxamates (Supuran and Scozzafava 2002a, 2002b). Only recently, several detailed studies on the possible modifications of the sulfonamido moiety, compatible with the retention of strong binding to the enzyme, have been reported (Briganti et al. 1996; Mincione
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