Anion inhibition studies of the α-carbonic anhydrases from Neisseria gonorrhoeae

The bacterial pathogen Neisseria gonorrhoeae encodes for an alpha-class carbonic anhydrase (CA, EC 4.2.1.1), NgCA, which was investigated for its inhibition with a series of inorganic and organic anions. Perchlorate and hexafluorophosphate did not significantly inhibit NgCA CO2 hydrase activity, whereas the halides, azide, bicarbonate, carbonate, stannate, perosmate, diphosphate, divanadate, perruthenate, and trifluoromethanesulfonate showed inhibition constants in the range of 1.3-9.6 mM. Anions/small molecules such as cyanate, thiocyanate, nitrite, nitrate, bisulphite, sulphate, hydrogensulfide, phenylboronic acid, phenylarsonic acid, selenate, tellurate, tetraborate, perrhenate, peroxydisulfate, selenocyanate, iminodisulfonate, and fluorosulfonate showed K(I)s in the range of 0.15-1.0 mM. The most effective inhibitors detected in this study were sulfamide, sulfamate, trithiocarbonate and N,N-diethyldithiocarbamate, which had K(I)s in the range of 5.1-88 mu M. These last compounds incorporating the CS2 (-) zinc-binding group may be used as leads for developing even more effective NgCA inhibitors in addition to the aromatic/heterocyclic sulphonamides, as this enzyme was recently validated as an antibacterial drug target for obtaining novel antigonococcal agents

Automated summary

The study investigated the inhibition of Neisseria gonorrhoeae's alpha-class carbonic anhydrase NgCA by various inorganic and organic anions. The most effective inhibitors were found to be sulfamide, sulfamate, trithiocarbonate, and N,N-diethyldithiocarbamate, showcasing the potential for developing novel antibacterial drugs.