Identification and inhibition of carbonic anhydrases from nematodes

Abstract

Carbonic anhydrases (CAs) are metalloenzymes, and classified into the evolutionarily distinct α, β, γ, δ, ζ, and η classes. α-CAs are present in many living organisms. β- and γ-CAs are expressed in most prokaryotes and eukaryotes, except for vertebrates. δ- and ζ-CAs are present in phytoplanktons, and η-CAs have been found in Plasmodium spp. Since the identification of α- and β-CAs in Caenorhabditis elegans, the nematode CAs have been considered as an emerging target in research focused on antiparasitic CA inhibitors. Despite the presence of α-CAs in both helminths and vertebrates, structural studies have revealed different kinetic and inhibition results. Moreover, lack of β-CAs in vertebrates makes this enzyme as an attractive target for inhibitory studies against helminthic infection. Some CA inhibitors, such as sulfonamides, have been evaluated against nematode CAs. This review article aims to present comprehensive information about the nematode CAs and their inhibitors as potential anthelminthic drugs.

Keywords:

• Acetazolamide
• carbonic anhydrase
• carbonic anhydrase inhibitors
• nematode
• sulfonamide

Declaration of interest

The authors declare that they have no competing interests.

To perform the original studies, RZE received a scholarship support from the Ministry of Science, Research and Technology, and National Institute of Genetic Engineering and Biotechnology of Islamic Republic of Iran. The studies were also supported by research grants from the Academy of Finland to SP, Finnish Funding Agency for Innovation (TEKES) to SP, Finnish Cultural Foundation (Pirkanmaa Regional Fund and Maili Autio Fund) to HRB and RZE, Sigrid Juselius Foundation to SP, Jane and Aatos Erkko Foundation to SP, Tampere Tuberculosis Foundation to SP, and Competitive Research Funding of the Tampere University Hospital.