An overview of carbohydrate-based carbonic anhydrase inhibitors

Figures & data

Figure 1. Schematic representation of zinc-binding CAI general structure in the CA binding site.

Figure 2. Chemical structures of Acetazolamide (AZA) 1, Brinzolamide 2 and Dorzolamide 3.

Figure 3. General structures of Topiramate analogues and anomeric sulfonamides, anomeric sulfamides and 6-sulfamoyl carbohydrates.

Figure 4. General structures of Topiramate thioureido-derivatives and anomeric sulfamates.

Figure 5. Interactions at the binding site in the structure of CA IX/57 complex (A), CA II/57 complex (B) and CA IX/55 complex (C) ²⁹. A) CA IX mimic (cyan) and 57 (magenta) (PDB ID: 4R5A). B) CA II (grey) and 57 (green) (PDB ID: 4R59). C) Overlay of the two conformations of 55 (purple and orange) with CA IX mimic. (PDB ID: 4R5B).

Figure 6. General structures of S-glycosyl sulfonamides and sulfenamides and thioureido-glycoconjugates.

Figure 7. General structures of amido phenyl sulfonamide glycoconjugates.

Figure 8. General structures of anomeric 1,4-disubstituted triazole sulfonamide glycoconjugates.

Figure 9. General structures of O-Glycosyl and the S-glycosyl 1,4-disubstituted triazoles, 1,4-disubstituted triazole saccharin-glycoconjugates and 1,5-disubstituted glycosyl triazoles.

Figure 10. General structure of coumarin glycosylated CA inhibitors.

Figure 11. General structure of C-glycosyl CA inhibitors.

Figure 12. General structure of dual-tail CA inhibitor glycoconjugates.

Figure 13. (A) Interactions at the binding site in the structure of CA II/332(magenta) complex (PDB ID: 4CQ0). (B) Surface representation of CA II/332 complex. The hydrophobic half of CA II is red and the hydrophilic half is blue to highlight the different interactions⁶⁷.

Table 1. Chemical structure, CA IX inhibitory activity, CA I/ CA IX selectivity profile of the best compound for each class of CA glycosidic inhibitors

Class	Structure	Ki CA IX (nM)	Selectivity ratio CA I/ CA IX	Ref.
Topiramate analogues		4.5	0.75	^18
Anomeric Sulfonamides		4	1.05	^22
Anomeric Sulfamides		9	86	^25
6-Sulfamoyl carbohydrates		8.4	674	^26

Table 2. Chemical structure, CA IX inhibitory activity, CA I/ CA IX selectivity profile of the best compound for each class of CA glycoconjugated inhibitors

Class	Structure	Ki CA IX (nM)	Selectivity ratio CA I/ CA IX	Ref.
Topiramate derivatives		10	1070	^28
Anomeric sulfamates		2	4750	^29
S-glycosyl derivatives		94	72	^31
Thioureido derivatives		2	2029	^32
Amidophenyl sulfonamides		700	17.4	^33
Glycosyl triazoles		6	60	^47
Coumarin derivatives		9	>11	^55
C-glycosyl derivatives		16	4	^66

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