Inhibition of β-carbonic anhydrases from Brucella suis with C-cinnamoyl glycosides incorporating the phenol moiety

Figures & data

Figure 1. Peracetylated C-glycosides (1–4) and fully deprotected derivatives (5–8).

Scheme 1. Preparation of C-cinnamoyl glycosides 1–8.

Table 1. Inhibition of hCA isoforms I, II and bsCA 1 and 2 with C-glycosides 1–8 and acetazolamide (AAZ; 5-acetamido-1,3,4-thiadiazole-2-sulfonamide) as standard, by a stopped-flow CO₂ hydrase assay*.

	K^i (µM)†
C-glycoside	hCA I‡	hCA II‡	bsCA I	bsCA II
1	8.5	7.0	0.92	0.71
2	5.7	3.9	5.65	2.68
3	5.1	7.1	0.68	0.63
4	9.3	5.5	7.18	4.85
5	6.8	7.8	3.45	0.78
6	3.7	8.8	7.92	4.75
7	3.6	3.1	6.54	0.83
8	5.5	6.8	5.43	2.80
AAZ	0.25	0.012	0.063	0.303

*All CAs are recombinant enzymes obtained in the authors’ laboratory as reported earlier5.

†Errors in the range of 5–10% of the reported value, from three different determinations.

‡From reference 11.

Table 2. Selectivity ratios of K_i for β-CAs compared to human α-CA isozymes I and II for the C-glycosides 1–8*.

	Selectivity
C-glycoside	hCA I/bsCAI	hCA I/bsCAII	hCA II/bsCAI	hCA II/bsCAII
1	9.24	11.97	7.61	9.86
2	1	2.13	0.69	1.45
3	7.50	8.09	10.44	11.27
4	1.29	1.92	0.77	1.13
5	1.97	8.72	2.26	10
6	0.47	0.78	1.11	1.85
7	0.55	4.38	0.47	3.73
8	1.01	1.96	1.25	2.43
AAZ	3.97	0.82	0.19	0.04

*The K_i ratios are indicative of isozyme selectivity for Brucella suis CAs in vitro and are calculated as K_i (human CA)/K_i(β-CA).

Joseph P, Turtaut F, Ouahrani-Bettache S, et al. Cloning, characterization, and inhibition studies of a β-carbonic anhydrase from Brucella suis. J Med Chem 2010;53:2277–85

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