The β-carbonic anhydrase from the malaria mosquito Anopheles gambiae is highly inhibited by sulfonamides

Bioorg Med Chem. 2015 May 15;23(10):2303-9. doi: 10.1016/j.bmc.2015.03.081. Epub 2015 Apr 7.


A β-carbonic anhydrase (CA, EC was cloned, purified and characterized from Anopheles gambiae, the mosquito species mainly involved in the transmission of malaria. The new enzyme, AgaCA, showed a significant catalytic activity for the physiologic reaction, CO2 hydration to bicarbonate and protons, with a kcat of 7.2×10(5)s(-1) and kcat/Km of 5.6×10(7)M(-1)s(-1), being thus similar to parasite β-CAs which were discovered earlier as drug targets for antifungal or anti-protozoan agents. An inhibition study of AgaCA with a panel of aromatic, aliphatic and heterocyclic sulfonamides allowed us to identify several low nanomolar inhibitors of the enzyme. Benzolamide and aminobenzolamide showed inhibition constants of 6.8-9.8nM, whereas a structurally related aromatic derivative, 4-(2-hydroxymethyl-4-nitrophenyl-sulfonamidoethyl)-benzenesulfonamide was the strongest inhibitor with a KI of 6.1nM. As β-CAs are not present in mammals, including humans, finding effective and selective A. gambiae CA inhibitors may lead to alternative procedures for controlling malaria by impairing the growth of its transmission vector, the mosquito.

Keywords: Anopheles gambiae; Carbonic anhydrase; Malaria; Sulfonamide; β-Class enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anopheles / chemistry*
  • Anopheles / classification
  • Anopheles / enzymology
  • Baculoviridae / genetics
  • Bicarbonates / chemistry
  • Carbon Dioxide / chemistry
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism
  • Cloning, Molecular
  • Gene Expression
  • High-Throughput Screening Assays
  • Insect Proteins / antagonists & inhibitors*
  • Insect Proteins / chemistry
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insecticides / chemistry*
  • Kinetics
  • Molecular Sequence Data
  • Phylogeny
  • Protons*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sf9 Cells
  • Spodoptera
  • Sulfanilamides / chemistry*


  • Bicarbonates
  • Carbonic Anhydrase Inhibitors
  • Insect Proteins
  • Insecticides
  • Protons
  • Recombinant Proteins
  • Sulfanilamides
  • Carbon Dioxide
  • Carbonic Anhydrases