An overview of novel antimicrobial carbonic anhydrase inhibitors.

INTRODUCTION

Four different genetic families of the enzyme carbonic anhydrase (CA, EC 4.2.1.1) are present in bacteria, α-, β-, γ- and ι-CAs. They play relevant functions related to CO, HCO/H ions homeostasis, being involved in metabolic biosynthetic pathways, pH regulation, and represent virulence and survival factors for bacteria in various niches. Bacterial CAs started to be considered druggable targets in the last decade, as their inhibition impairs survival, growth, and virulence of these pathogens.

AREAS COVERED

Significant advances were registered in the last years for designing effective inhibitors of sulfonamide type for α-CA, α-CA, vacomycin-resistant enterococci (VRE) α- and γ-CAs, for which the in vivo validation has also been achieved. MIC-s in the range of 0.25-4.0 µg/mL for wild type and drug resistant strains, and of 0.007-2.0 µg/mL for VRE were observed for some 1,3,4-thiadiazole-2-sulfonamides, and acetazolamide was effective in gut decolonization from VRE.

EXPERT OPINION

Targeting bacterial CAs from other pathogens, among which , , , serovar Typhimurium, , , , , , , , , , may lead to novel antibacterials devoid of drug resistance problems.