Herbicide oryzalin inhibits human carbonic anhydrases in vitro

Abstract

Herbicides of the dinitroaniline chemical class, widely used oryzalin and trifluralin, and also nitralin were tested as inhibitors of recombinant human carbonic anhydrases (CAs). Oryzalin bound and inhibited 11 out of 12 catalytically active CA isoforms present in the human body with the affinities in the same range as clinically used CA drugs, while no effect was detected for the other two compounds. Binding of all three herbicides was examined by fluorescence-based thermal shift assay, isothermal titration calorimetry, and the inhibition of carbon dioxide hydratase activity. During the last decade, dinitroaniline compound-based therapies against protozoan diseases are being developed. Therefore, it is important to investigate their potential off-target effects, including human CAs.

Keywords: carbonic anhydrase; herbicide; isothermal titration calorimetry; oryzalin; trifluralin.