New insights into the selective inhibition of the β-carbonic anhydrases of pathogenic bacteria Burkholderia pseudomallei and Francisella tularensis: a proteochemometrics study
- 166 Downloads
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.
Keywordsβ-carbonic anhydrase Proteochemometrics Selectivity Burkholderia pseudomallei Francisella tularensis
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
- 2.Ozensoy Guler O, Capasso C, Supuran CT (2016) A magnificent enzyme superfamily: carbonic anhydrases, their purification and characterization. J Enzyme Inhib Med Chem 31:689–694Google Scholar
- 7.Supuran CT (2013) Carbonic anhydrases: from biomedical applications of the inhibitors and activators to biotechnological use for CO2 capture. Med Chem 28:229–230Google Scholar
- 8.Bejaoui M, Pantazi E, De Luca V, Panisello A, Folch-Puy E, Hotter G et al (2015) Carbonic anhydrase protects fatty liver grafts against ischemic reperfusion damage. PLoS One 10:1–16Google Scholar
- 11.Gillard JJ, Laws TR, Lythe G, Molina-París C (2014) Modeling early events in Francisella tularensis pathogenesis. Front Cell Infect Microbiol 11:169–178Google Scholar
- 16.Currie BJ (2010) Burkholderia pseudomallei and Burkholderia mallei: melioidosis and glanders. In: Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. Churchill Livingstone Elsevier, Philadelphia, pp 2869–2885Google Scholar
- 32.Version, S., 6.9, Tripos Associates, St. Louis, Mo, 2001Google Scholar
- 38.Beasley D, Bull DR, Martin RR (1993) An overview of genetic algorithms: part 1, fundamentals. University computing 15:56–69Google Scholar
- 42.Gramatica P (2007) Principles of QSAR models validation: internal and external. Mol Inf 26:694–701Google Scholar
- 43.Tropsha A, Gramatica P, Gombar VK (2003) The importance of being earnest: validation is the absolute essential for successful application and interpretation of QSPR models. Mol Inf 22:69–77Google Scholar