New insights into the selective inhibition of the β-carbonic anhydrases of pathogenic bacteria Burkholderia pseudomallei and Francisella tularensis: a proteochemometrics study.

Nowadays, antibiotic resistance has turned into one of the most important worldwide health problems. Biological end point of critical enzymes induced by potent inhibitors is recently being considered as a highly effective and popular strategy to defeat antibiotic-resistant pathogens. For instance, the simple but critical β-carbonic anhydrase has recently been in the center of attention for anti-pathogen drug discoveries. However, no β-carbonic anhydrase selective inhibitor has yet been developed. Available β-carbonic anhydrase inhibitors are also highly potent with regard to human carbonic anhydrases, leading to severe inevitable side effects in case of usage. Therefore, developing novel inhibitors with high selectivity against pathogenic β-carbonic anhydrases is of great essence. Herein, for the first time, we have conducted a proteochemometric study to explore the structural and the chemical aspects of the interactions governed by bacterial β-carbonic anhydrases and their inhibitors. We have found valuable information which can lead to designing novel inhibitors with better selectivity for bacterial β-carbonic anhydrases.