Carbonic anhydrase inhibitors: in vitro inhibition of α isoforms (hCA I, hCA II, bCA III, hCA IV) by flavonoids

Figures & data

Figure 1.  Schematic representation for the three main CA inhibition mechanisms: (A) Sulfonamides (and their isosteres, sulfamate, and sulfamide) substitute the fourth zinc ligand and bind in tetrahedral geometry of the metal ion¹²; (B) Inorganic anion inhibitors (thiocyanate as an example) add to the metal ion coordination sphere leading to trigonal bipyramidal adducts¹²; (C) Phenols anchor to the Zn(II) coordinated water molecule/hydroxide ion¹³; (D) Coumarins (hydrolyzed in situ to 2-hydroxycinnamic acids) occlude the entrance of the active site cavity, interacting both with hydrophilic and hydrophobic amino acid residues. The inhibitor does not interact at all with the catalytically crucial Zn(II) ion which is coordinated by three His residues and a water molecule^10,11.

Table 1.  K_I values (μM) for compound 1–8, EZA, ZNA and AZA of some α-carbonic anhydrase isoforms in human (h) and bovine (b). ^aRef ²⁹.

Compound	hCA I	hCA II	bCA III	hCA IV
Quercetin (1)	3.6	2.4	9.1	13.8
Catechin (2)	6.8	6.2 ^a	2.2	5.6
Apigenin (3)	4.1	2.7	11.6	9.1
Luteolin (4)	2.2	0.74	5.4	4.4
Morin (5)	12.8	4.4	21.3	15.7
Phenol (6)	17.3	7.4	4.6	14.3
Resorcinol (7)	828	9.4	219	634
Catechol (8)	4014	11.4	6.5	11.9
EZA	3.7	0.32	9.4	0.84
ZNA	14.8	1.1	8.5	38.4
AZA	36.2	0.37	263	0.58

Figure 2.  Structures of common used CA inhİbitors.

Figure 3.  Structures of tested compounds 1–8.

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