Kinetic and in silico analysis of thiazolidin-based inhibitors of α-carbonic anhydrase isoenzymes

Figures & data

Figure 1.  Chemical structures of commonly used medical sulfonamides.

Figure 2.  Chemical structures of tested compounds.

Figure 3.  Compound 6b at hCA-I.

Figure 4.  Compound 6b at hCA-II.

Table 1.  hCA I and II inhibition data (K_I) with compounds 1–10, ZNA and AZA, by an esterase assay with 4-nitrophenylacetate as substrate.

Compound	hCA I (μM)	hCA II (μM)
1	6.8	1.34
2	47.5	2.48
3	5.38	1.36
4	5.51	1.32
5a	27.5	2.29
5b	29.4	3.59
6a	5.58	0.93
6b	4.43	0.81
7^a	42.4	37.5
8^a	37.3	23.1
9^a	14.6	0.51
10^a	25.7	0.73
ZNA^b	14.8	1.07
AZA	36.2	0.37

Mean from at least three determinations. Errors in the range of 1–3% of the reported value (data not shown).

^aFrom ref.⁶.

^bFrom ref.¹⁰.

Table 2.  Molecular docking binding scores of compounds 1–6b and ZNA within the hCA I and II active site.

Molecule	Binding score at hCA-I (kcal/mol)	Binding score at hCA-II (kcal/mol)
1	−6.34	−8.45
2	−5.26	−8.18
3	−6.27	−8.42
4	−6.40	−8.66
5a	−5.90	−8.72
5b	−5.71	−7.87
6a	−6.39	−8.48
6b	−6.60	−9.09
ZNA	−7.10	−10.89