Inhibition of the β-carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with sulphonamides

Figures & data

Figure 1. (A) TvaCA1 dimeric structure, with the two monomers shown in green and red, respectively¹⁰. (B) Active site of the enzyme, with the zinc ion (gray sphere) coordinated by two Cys, one His and one water molecule/hydroxide ion (shown in red). Residues numbering as described by Urbański et al.¹⁰.

Figure 2. Sulphonamides 1–24 and clinically used agents AAZ–HCT investigated as TvaCA1 inhibitors.

Table 1. Inhibition of human isoform hCA II, for comparison, and of the protozoan enzyme TvaCA1 with sulphonamides 1–24 and the clinically used drugs AAZ–HCT, measured by a CO₂ hydrase, stopped-flow assay.²¹

Inhibitor/enzyme	KI^a (nM)
	hCA II^b	TvaCA1^c
Class	α	β
1	300	3246
2	240	4742
3	8	3559
4	320	3599
5	170	>50,000
6	160	>50,000
7	60	4282
8	110	>50,000
9	40	>50,000
10	54	4536
11	63	>50,000
12	75	>50,000
13	60	1889
14	19	3987
15	80	2027
16	94	>50,000
17	125	>50,000
18	46	>50,000
19	33	4528
20	2	>50,000
21	11	3450
22	46	>50,000
23	33	>50,000
24	30	>50,000
AAZ	12	391
MZA	14	3827
EZA	8	283
DCP	38	>50,000
DZA	9	>50,000
BRZ	3	>50,000
BZA	9	>50,000
TPM	10	>50,000
ZNS	35	>50,000
SLP	40	>50,000
IND	15	>50,000
VLX	43	>50,000
CLX	21	>50,000
SLT	9	>50,000
SAC	5959	>50,000
HCT	290	>50,000

^a Errors in the range of 5–10% of the shown data, from 3 different assays.

^b Human recombinant isozyme, measured by stopped flow CO₂ hydrase assay method.

^c Recombinant protozoan enzyme, measured by stopped flow CO₂ hydrase assay method, this study.

Urbański LJ, Di Fiore A, Azizi L, et al. S. Biochemical and structural characterisation of a protozoan beta-carbonic anhydrase from Trichomonas vaginalis. J Enzyme Inhib Med Chem 2020; 35:1292–9.

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Khalifah RG. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. J Biol Chem 1971;246:2561–73.

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