Catechol-based inhibitors of bacterial urease

Abstract

Targeted covalent inhibitors of urease were developed on the basis of the catechol structure. Forty amide and ester derivatives of 3,4-dihydroxyphenylacetic acid, caffeic acid, ferulic acid and gallic acid were obtained and screened against Sporosarcinia pasteurii urease. The most active compound, namely propargyl ester of 3,4-dihydroxyphenylacetic acid exhibited IC₅₀ = 518 nM andk_inact/K_i = 1379 M^-1 s^-1. Inhibitory activity of this compound was better and toxicity lower than those obtained for the starting compound - catechol. The molecular modelling studies revealed a mode of binding consistent with structure-activity relationships.