Relations Between Structure and Biological Activity of Sulfonamides

Carbonic anhydrase inhibitors

“…Among the active structures found by Krebs were also the azodyes 2 (prontosil red) and 3, derived from sulfanilamide. The early stages of CAIs development have thouroughly been reviewed by Maren,21,22 whereas literature till 1993 was reviewed by Supuran 26 and more incompletely (up to 1996) by Mansoor et al 27 Thus, in this review we will concentrate on the recent developments in this field that led to important advances in the design of topically acting antiglaucoma sulfonamides, isozyme-specific inhibitors, inhibitors with modified sulfonamide moieties, antitumor sulfonamides, as well as diagnostic tools and biosensors based on this class of pharmacological agents.…”

“…2,21 Still, none of the clinically used inhibitors 4-7 (or other structurally related investigational agents) 21 proved to be effective when administered topically in reducing elevated IOP, and thus, for a long period, it was considered that sulfonamide CAIs cannot be administered via topical route. 22 In a classical study, Maren's group then showed that this is principally due to the unappropriate physicochemical properties of the existing CAIs available at that moment, and put the basis for the discovery of the topically acting sulfonamides: the first such drug, dorzolamide (8), 29 entered in clinics in 1995, and the second one (structurally related to dorzolamide)-brinzolamide (9) 30 entered in clinics in 1999. Thus, in addition to the systemically acting inhibitors 4-7, the clinical antiglaucoma armamentarium comprises these two new drugs, which show much less side effects as compared to the first drugs mentioned above, but which also basically inhibit all the physiologically relevant CA isozymes (Table II).…”

Synthesis and biological evaluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents

“…Anti-inflammatory, analgesic, and antipyretic activities for some thiazolyl and benzothiazolyl derivatives are also known. 7,8 On the other hand, sulfonamides have a variety of biological activities such as antibacterial, [9][10][11] insulin releasing, 12 carbonic anhydrase inhibitory, 13,14 anti-inflammatory, 15 and antitumor 16 activities. These findings encouraged us to explore the synthesis of sulfonamides containing thiazole/benzothiazole moieties and to examine their antibacterial and antifungal properties.…”

Two point mutations convert a catalytically inactive carbonic anhydrase‐related protein (CARP) to an active enzyme

“…Additional evidence is provided by the strong inhibition of the activity by acetazolamide, a powerful and specific CA inhibitor [16]. After the initiation of our study, Kiefer et al [17] have shown that the replacement of Gln 92 with Glu in human CA II has only a marginal effect on zinc affinity.…”