Benzylaminoethylureido-Tailed Benzenesulfonamides Show Potent Inhibitory Activity Against Bacterial Carbonic Anhydrases

A series of benzylaminoethylureido-tailed benzenesulfonamides was analyzed for their inhibition potential against bacterial carbonic anhydrases (CAs) such as VhCA alpha, beta, and gamma from Vibrio cholerae, and BpsCA beta and gamma-CAs from Burkholderia pseudomallei. Growing drug resistance against antibiotics demands alternative targets and mechanisms of action. As CA is essential for the survival of bacteria, such enzymes have the potential for developing new antibiotics. Most of the compounds presented excellent inhibition potential against VhCA gamma compared to alpha and beta, with K-i values in the range of 82.5-191.4 nM. Several sulfonamides exhibited excellent inhibition against BpsCA beta with K-i values in the range of 394-742.8 nM. Recently it has been demonstrated that sufonamide CA inhibitors are effective against vancomycin-resistant enterococci. These data show that CA inhibition of pathogenic bacteria may lead to a new class of antibiotics.