Inhibition of α-, β-, γ-, δ-, ζ- and η-class carbonic anhydrases from bacteria, fungi, algae, diatoms and protozoans with famotidine

Figures & data

Figure 1. hCA I adduct of famotidine (FAM). (a) Overall structure. (b) Active site details, with the Zn(II) ion (gray sphere), its three His ligands and the inhibitor in green.

Figure 2. hCA II adduct of famotidine (FAM). (a) Overall structure. (b) Active site details, with the Zn(II) ion (gray sphere), its three His ligands and the inhibitor in green.

Table 1. Inhibition data against bacterial, diatom, fungal, protozoan, insect and human CAs with famotidine (FAM) and acetazolamide (AAZ) by a stopped flow CO₂ hydrase assay²².

KI (nM)*
	Organism	Enzyme class	FAM	AAZ
VchCAα	Bacterium	Α	72.3	6.8
VchCAβ	Bacterium	Β	83917	451
VchCAγ	Bacterium	Γ	5321	473
SspCA	Bacterium	Α	230	4.5
SazCA	Bacterium	Α	124	0.9
Rv3274	Bacterium	Β	1265	104
BpsCAβ	Bacterium	Β	8271	745
BpsCAγ	Bacterium	Γ	8293	149
PhaCAγ	Bacterium	Γ	66.8	403
CpsCAγ	Bacterium	Γ	89.0	502
NcoCAγ	Cyanobacterium	Γ	1695	75.8
TweCAδ	Diatom	Δ	408	83
TweCA Cd	Diatom	Ζ	90.7	69
TweCA Zn	Diatom	Ζ	22.1	58
MgaCA	Fungus	Β	42109	40000
Can2	Fungus	Β	107	10.5
CgNce103	Fungus	Β	13.6	11
TcCA	Protozoan	Α	5707	61.6
PfCA	Protozoan	η	142	170
AgaCA	Insect	Β	397	26
hCA I**	Human	Α	922	250
hCA II**	Human	Α	58.0	12.1

*Mean from three different assays, by a stopped flow technique (errors were in the range of ±5–10% of the reported values).

**From Ref.²⁶.

(a) Monti SM, Maresca A, Viparelli F, et al. Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic anhydrases from Cryptococcus neoformans, Candida albicans and Candida glabrata. Bioorg Med Chem Lett 2012;22:859–62. (b) De Simone G, Supuran CT. (In)organic anions as carbonic anhydrase inhibitors. J Inorg Biochem 2012;111:117–29.

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