Skip to content
2000
Volume 16, Issue 29
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

The facultative intracellular pathogen and zoonotic agent Brucella sp. possesses two carbonic anhydrases (CAs, EC 4.2.1.1), termed bsCA I and bsCA II (in Brucella suis), belonging to the β-class of these metalloproteins. These zinc enzymes, present in many other pathogenic bacteria, have been considered recently as potential antibacterial targets. The catalytic activity of bsCA II is higher than that of bsCA I (for the conversion of CO2 to bicarbonate). Both enzymes were inhibited by the well-studied inhibitor acetazolamide, a sulfonamide drug. A library of 41 sulfonamides and one sulfamate, among which were 13 clinically tested drugs, was used for inhibition studies with bsCA I and II. These compounds were generally much more potent inhibitors of bsCA I (KIs of 17-75 nM) than of bsCA II (KIs of 84-923nM). However, certain glycosidic sulfonamide derivatives exhibited the same strong inhibitory activity on both bsCA I and bsCA II (KIs of 8.9-20 nM). Furthermore, at least one of these glycosylsulfonamides showed a significant inhibition of B. suis growth after 8-11 days of culture in minimal medium. In conclusion, as β-CAs of Brucella are susceptible to inhibition by a wide range of aromatic and heteroaromatic sulfonamides, they may represent novel targets for the development of clinically useful antibacterial agents.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/138161210793429850
2010-10-01
2025-05-07
Loading full text...

Full text loading...

/content/journals/cpd/10.2174/138161210793429850
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test