Coumarins effectively inhibit bacterial α-carbonic anhydrases

Figures & data

Figure 1. Surface representation of hCA II in adduct with the superimposed hydrolized (and active) coumarin species (cyan from 5BNL, green from PDB 3F8E). The hydrophobic half of the active site is coloured in red, the hydrophilic one in blue. His64, the proton shuttle residue, is in green.

Table 1. Inhibition data of hCA I and II and bacterial enzymes NgCAα and VchCAα using AAZ as standard drug by a stopped-flow CO₂ hydrase assay at 6 h incubation time between enzyme and inhibitor.

Name	Structure	Ki (µM)^a
		hCA I	hCA II	NgCAα	VchCAα
1		160.0 (3.1)^b	600.0 (9.2)^b	81.6	94.7
2		192.0	683.0	92.4	77.5
3		263.5	690.6	77.1	68.5
4		393.5	513.1	94.7	92.2
5		489.8	625.2	110.0	289.5
6		646.3	485.7	70.9	71.1
7		939.6	733.5	97.1	95.0
8		516.5	558.9	28.6	53.9
9		948.9	646.2	42.5	39.8
10		137.0	296.5	68.0	66.8
11		748.9	875.6	469.5	438.7
12		181.8	758.4	77.6	66.0
13		900.1	961.2	394.5	431.9
14		469.7	786.2	394.5	302.7
AAZ	–	0.25	0.012	0.075	0.0068

^aMean from three different assays, by a stopped flow technique (errors were in the range of ± 5–10% of the reported values); ^bData from ref.¹³, with a longer incubation time between enzyme and coumarin.

(a) Maresca A, Temperini C, Vu H, et al. Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors. J Am Chem Soc 2009;131:3057–62.

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(b) Maresca A, Temperini C, Pochet L, et al. Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. J Med Chem 2010;53:335–44.

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