Diversely N-substituted benzenesulfonamides dissimilarly bind to human carbonic anhydrases: crystallographic investigations of N-nitrosulfonamides

Figures & data

Figure 1. Structures of benzenesulfonamide 1 and N-substituted sulphonamides 2–5.

Scheme 1. Synthetic route to obtain the N-nitrosulfonamide derivative 4.

Table 1. Inhibition data of human CA isoforms I, II, IV, IX, and XII with compounds 1–4 and AAZ^17,19,20.

KI (µM)^a
Cmp	hCA I	hCA II	hCA IV	hCA IX	hCA XII
1^b	0.086	0.101	7.96	0.097	0.090
2^c	2.73	5.47	24.6	60.3	1.53
3^c	>1000	8.96	39.5	64.3	8.32
4^d	58.3	64.2	11.0	4.5	3.9
AAZ	0.25	0.012	0.074	0.026	0.006

^a Mean from three different assays, by a stopped flow technique (errors were in the range of ±5–10% of the reported values).

^b Inhibition data from Ref.¹⁹

^c Inhibition data from Ref.¹⁶

^d Inhibition data from Ref.¹⁷

Figure 2. (A) Active site region of the 4-hCA II complex (PDB: 8BZZ). Hydrogen bonds (red), van der Waals interactions (blue), and zinc interactions (green) are also shown. (B) Structural superposition between 4-hCA II (green) and 2-hCA II (magenta, PDB: 3T5U)¹⁷ bound to the active site of protein. (C) Structural superposition between 4-hCA II (green) and 1-hCA II (cyan, PDB: 2WEJ)²¹ bound to the active site of protein.

Figure 3. (A) Structural superposition between 4-hCA II (green) and 3-hCA II (purple, PDB: 3T5Z)¹⁷ bound to the active site of protein. (B) Structural superposition between 4-hCA II (green) and 5-hCA II (orange, PDB: 7AEQ)²³ bound to the active site of protein. (C) Structural superposition between 4-hCA II (green), 3-hCA II (purple), and 5-hCA II (orange) bound to the active site of protein.

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