Abstract
After being rather neglected as a research field in the past, carbonic anhydrase activators (CAAs) were undoubtedly demonstrated to be useful in diverse pharmaceutical and industrial applications. They also improved the knowledge of the requirements to selectively interact with a CA isoform over the others and confirmed the catalytic mechanism of this class of compounds. Amino acid and amine derivatives were the most explored in in vitro, in vivo and crystallographic studies as CAAs. Most of them were able to activate human or non-human CA isoforms in the nanomolar range, being proposed as therapeutic and industrial tools. Some isoforms are better activated by amino acids than amines derivatives and the stereochemistry may exert a role. Finally, non-human CAs have been very recently tested for activation studies, paving the way to innovative industrial and environmental applications.
Highlights
Compounds 64 and 65 in particular revealed to be highly selective for the isoform Carbonic Anhydrases (CAs) II and VII, respectively, opening new perspectives in the design of potent and selective carbonic anhydrase activators (CAAs) based on the amino alcohol scaffold, as valid alternative to amines and amino acids [72] (Figure 9)
Despite most of the CAAs showed rather flat activating efficacy with kinetic data (KA) values ranging between 3.9 and 45.6 μM, the results suggested that small structural changes in the compounds can induce important modifications of their CA activating properties
The field of carbonic anhydrase activators has been underexplored so far due to the skepticism that scientists experienced regarding an enzyme which usually improves the rate of an important biological reaction
Summary
Amino acids (AAs) do possess significant roles in Medicinal Chemistry either as free drugs or being constitutive elements within more complex structures in natural products or within synthetic compounds [1,2,3]. The main advantage in dealing with amino acids is to acquire readily available building blocks bearing features such as: (i) orthogonal protecting groups conveniently adjustable by means of well-established synthetic methods (i.e., acylation, alkylation among others); (ii) additional moieties usable to meet the synthetic needs and (iii) chiral centers, with major optical differences between the series produced by eukaryotic or prokaryotic organisms. More importantly all such features are packed into low molecular weight compounds with beneficial effects on their handling and treatment. The purpose of this work is to offer an up-to-date comprehensive overview on AAs, BAs and their synthetic analogues which act in vitro as activators of the metalloenzymes Carbonic Anhydrases (CAs; EC 4.2.1.1) considering this topic is acquiring increased attention among the scientific community for biomedical as well as technological applications
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
