Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase

Figures & data

Table 1. Human (h) hCA I, II and yeast (S. cerevisiae) ScCA inhibition data with phenols 1–13 by a stopped flow CO₂ hydrase assay31.

		Ki (µM)*	Ki (µM)*	Ki (nM)*
Compound	NR1R2	hCA I	hCA II	ScCA
1	–	0.78	12.5	76.5
2	–	1.77	10.8	65.8
3	Me2N	23.5	29.8	23.5
4	Et2N	7.76	26.9	77.1
5	(CH2)4N	5.40	34.7	4.9
6	(CH2)5N	17.9	41.5	65.0
7	MeN(CH2CH2)N	3.35	14.7	76.5
8	Me2N	9.01	34.9	90.1
9	Et2N	4.05	43.1	81.9
10	(CH2)4N	2.36	45.8	85.8
11	(CH2)5N	1.88	48.0	79.1
12	MeN(CH2CH2)N	2.01	47.7	79.5
13	O(CH2CH2)N	0.91	52.4	95.4
AAZ	–	0.25	0.012	82.6

*Mean from three different assays (errors in the range of ±10% of the reported values, data not shown).

Figure 1. Alignment of the amino acid sequences of selected β-CAs from four species. The S. cerevisiae numbering system was used. Zinc ligands (amino acids: 57, 112 and 115) are indicated in red whereas the catalytic dyad (amino acids 59 and 61) typical of β-CAs in blue. The asterisk (*) indicates identity at a position; the symbol (:) designates conserved substitutions, while (·) indicates semi-conserved substitutions. Multiple alignment was performed with the program Clustal W, version 2.1 (http://www.ebi.ac.uk/services/proteins). Sequence accession numbers are indicated in Figure 2.

Figure 2. Phylogenetic tree of the beta CAs from selected eukaryotic and prokaryotic species. The tree was constructed using the program PhyML 3.0 (http://www.atgc-montpellier.fr/phyml/). Organisms and sequence accession numbers are as follows: Schizosaccharomyces pombe (CAA21790); Brucella suis 1330 (NP_699962.19); Burkholderia thailandensis Bt4 (ZP_02386321); Coccomyxa sp. (AAC33484.1); Chlamydomonas reinhardtii (XP_001699151.1); Acinetobacter baumannii (YP_002326524); Porphyromonas gingivalis ATCC 33277 (YP_001929649.1); Myroides injenensis (ZP_10784819); Zea mays (NP_001147846.1); Vigna radiata (AAD27876); Flaveria bidentis, isoform I (AAA86939.2); Arabidopsis thaliana (AAA50156); Helicobacter pylori (BAF34127.1); Legionella pneumophila 2300/99 (YP_003619232); Escherichia coli (ACI70660); Saccharomyces cerevisiae (GAA26059); Dekkera bruxellensis AWRI1499 (EIF49256).

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

 PubMed Web of Science ®Google Scholar