Inhibitory effects of sulfenimides on human and bovine carbonic anhydrase enzymes

Figures & data

Figure 1. Structures of tested compounds.

Table 1. CA enzyme inhibition data with sulfenimides (KI values).

Inhibitor	KI (μM)^a
	hCA I	hCA II	bCA
1a	0.0585	0.0515	NA
1b	NA	NA	NA
1c	0.0379	0.060	NA
1d	0.1194	0.152	NA
1e	0.0321	0.1426	38.50
1f	0.0230	0.0440	20.57
1g	0.0408	0.0520	NA
1h	0.0503	0.0617	197.22
1i	0.0254	0.0546	265.96
AZA 35	0.25	0.012	40 mM

^aErrors in the range of standart error, from 3 different assays.

Table 2. Pharmacokinetic properties of the compounds obtained from SwissADME database.

Pharmacokinetic Properties	Compounds No
	1a	1b	1c	1d	1e	1f	1g	1h	1i
Gastrointestinal absorption	High	High	High	High	High	High	High	High	High
Blood-brain barrier permeant	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	No
P-glycoprotein substrate	No	No	No	No	No	No	No	No	No
Cytochrome P450 1A2 inhibitor	Yes	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes
Cytochrome P450 2C19 inhibitor	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No
Cytochrome P450 2C9 inhibitor	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Cytochrome P450 2D6 inhibitor	No	No	No	No	No	No	No	No	High
Cytochrome P450 3A4 inhibitor	No	No	Yes	No	No	No	No	No	No
Log Kp (skin permeation)	–6.11 cm/s	–5.94 cm/s	–6.32 cm/s	–6.51 cm/s	–5.87 cm/s	–6.10 cm/s	–6.24 cm/s	–5.97 cm/s	No

Figure 2. Activity %-[C₁₄H₈BrNO₂S (µM) (1f)] regression analysis graph for hCA-I in the presence of five different concentrations.

Figure 3. Activity %-[C₁₄H₈BrNO₂S (µM) (1f)] regression analysis graph for hCA-II in the presence of five different concentrations.

Figure 4. Activity %-[C₁₄H₈BrNO₂S (µM) (1f)] regression analysis graph for bCA in the presence of five different concentrations.

Figure 5. The BOILED-Egg predictive model for sulfenimide derivatives. The white region is the physicochemical space of molecules with highest probability of being absorbed by the gastrointestinal tract, and the yellow region is the physicochemical space of molecules with highest probability to permeate to the brain. Yolk and white areas are not mutually exclusive.

Carta F, Vullo D, Maresca A, Scozzafava A, Supuran CT. New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoformmII. Bioorg Med Chem Lett. 2012;22(6):2182–2185.

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