Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds

Figures & data

Table 1. K_I values for the in vitro inhibition of hCA I, hCA II and IX with compounds 1–10, NK-154, NK-168 and AZA.

	KI (μM)*
Inhibitor	hCA I	hCA II	hCA IX
Phenol (1)^a	10.2	5.50	8.80
Catechol (2)^a	4003	9.9	115
Resorcinol (3)^a	795	7.7	69.7
Pyrogallol (4)^b	7.41	0.54	–
Salicylic acid (5)^a	9.9	7.1	78.7
o-Coumaric acid (6)^c	3.1	9.2	>1000
Dobutamine (7)^c	1.92	0.48	9.82
Curcumin (8)^c	2.41	0.38	4.05
NK-154	0.074	>1000	0.481
NK-168	0.068	>1000	0.490
9^d	8.03	3.83	7.15
10^d	3.34	350	21
AZA^a	0.25	0.012	0.025

*Mean from at least three determinations. Errors in the range of ∼2% of the reported value (data not shown).

^aFrom ref. 19.

^bFrom ref. 3.

^cFrom ref. 21.

^dFrom ref. 20.

Figure 1. Chemical structures of some carbonic anhydrase inhibitor phenolic compounds.

Figure 2. Chemical structures of tested compounds.

Figure 3. 2D docking poses of NK-154 and NK-168 into the hCAI, hCA II and hCAIX receptors. Polar, hydrophobic and charged domains were highlighted by different colors as shown in diagram legend.

Figure 4. 3D docking poses of NK-154 and NK-168 into the hCAI, hCA II and hCA IX receptors. Key amino acid residues were determined in the 3D positions in active sites.

Table 2. Docking score values of selected ligands against hCA I, hCA II and hCA IX.

	hCA I	hCA II	hCA IX
Compound	IFD results (kcal/mole)	IFD results (kcal/mole)	IFD results (kcal/mole)
Phenol (1)	−5.36	−5.72	−5.62
Catechol (2)	−6.04	−6.28	−5.78
Resorcinol (3)	−6.01	−6.74	−7.24
NK-154	−7.87	−8.69	−9.87
NK-168	−7.19	−9.02	−9.82
AZA	−5.82	−7.85	−7.39