Mono- and di-thiocarbamate inhibition studies of the δ-carbonic anhydrase TweCAδ from the marine diatom Thalassiosira weissflogii

Abstract

The inhibition of the δ-class carbonic anhydrase (CAs, EC 4.2.1.1) from the diatom Thalassiosira weissflogii, TweCAδ, was investigated using a panel of 36 mono- and di-thiocarbamates chemotypes that have recently been shown to inhibit mammalian and pathogenic CAs belonging to the α- and β-classes. TweCAδ was not significantly inhibited by most of such compounds (K_I values above 20 µM). However, some aliphatic, heterocyclic, and aromatic mono and di-thiocarbamates inhibited TweCAδ in the low micromolar range. For some compounds incorporating the piperazine ring, TweCAδ was effectively inhibited (K_Is from 129 to 791 nM). The most effective inhibitors identified in this study were 3,4-dimethoxyphenyl-ethyl-mono-thiocarbamate (K_I of 67.7 nM) and the R-enantiomer of the nipecotic acid di-thiocarbamate (K_I of 93.6 nM). Given that the activity and inhibition of this class of enzyme have received limited attention until now, this study provides new molecular probes and information for investigating the role of δ-CAs in the carbon fixation processes in diatoms, which are responsible for significant amounts of CO₂ taken from the atmosphere by these marine organisms.

Keywords:

• Carbonic anhydrase
• metalloenzymes
• mono-thiocarbamate
• di-thiocarbamate
• Thalassiosira weissflogii

Disclosure statement

The authors do not declare any conflict of interest.

Additional information

Funding

This research was financed in part by the Australian Research Council [DP160102681].