Discovered 80 year ago, in 1933, carbonic anhydrases (CAs) were intensely investigated due to the biomedical applications of their inhibitors and because these enzymes (characterized by the presence of a large number of isoforms in most organismsCitation1–7) are involved in many crucial physiologic and pathologic processesCitation1,Citation2. CAs are metalloenzymes, and they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate and protonsCitation1–9. All of them are essential molecules/ions in many important physiologic processes in all life kingdoms (Bacteria, Archaea and Eukarya), throughout the tree of life, and for this reason, relatively high amounts of these enzymes are present in different tissues/cell compartments of most investigated organismsCitation1–10. Drugs interfering with the activity of the CAs have been clinically used for almost 60 years, most of them belonging to the sulfonamide classCitation1,Citation3,Citation9,Citation10.
Inhibition of the CAs has pharmacologic applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but their use is also emerging for designing anti-infectives, i.e., antifungal and antibacterial agents with a novel mechanism of actionCitation1,Citation3,Citation11–13. As a consequence, the drug design of CA inhibitors (CAIs) is a highly dynamic field. Sulfonamides and their isosteres (sulfamates/sulfamides) constitute the main class of CAIs, which bind to the metal ion from the enzyme active site, and have been in clinical use for decadesCitation1. Lately other families of CAIs were reported, which possess a distinct mechanism of action compared to the sulfonamides: the phenols, polyamines, some carboxylates and sulfocoumarins, were shown to anchor to the zinc-coordinated water molecule from the enzyme active siteCitation1,Citation12–16. Coumarins and some lactones were shown to be pro-drug inhibitorsCitation1,Citation17,Citation18, binding in hydrolyzed form at the entrance of the active site cavity. Novel drug design strategies have been reported principally based on the tail approachCitation19 for obtaining all these types of CAIs, which exploit more external binding regions within the enzyme active site (in addition to coordination to the metal ion), leading thus to isoform-selective compoundsCitation20. Sugar-based tails as well as click chemistry were the most fruitful developments of the tail approachCitation21,Citation22. Promising compounds that inhibit CAs from bacterial and fungal pathogensCitation23,Citation24, of the dithiocarbamateCitation25, phenol and carboxylate types have also been reportedCitation26 lately.
But recently, due to the steep increase in the CO2 concentration in the atmosphere and the green house effects of this gasCitation27, a lot of research concentrated on the biotechnologic use of various CAs, some of which were isolated from not so common vertebratesCitation14,Citation15 and even extremophilic bacteriaCitation28–30, with the goal of using the high catalytic activity of such enzymes for capturing CO2. Such a “green”, novel approach for CO2 capture may resolve the stringent problem of global warming in an efficient and elegant manner.
All these aspects and many others which are impossible to mention for lack of space, were dealt with at the 9th International CA Conference which was held in Antalya, Turkey, in April 2012. This issue of our journal is dedicated to some of the most interesting contributions presented at this conference. I also take the opportunity to announce that the next CA meeting will be held in Maastricht, the Netherlands, in 2015, but a mid-term meeting will be organized in Naples, Italy later in 2013.
The important advances in the field, the high number of good quality publications on all aspects of CA research, and all the international meetings which are being organized frequently, testify the crucial role that these enzymes may have both for future biomedical as well as biotechnologic applications. After all, not such “a boring enzyme” any longer (as CAs have been described in the 80s and 90s by some members of the scientific community, worried of the side effects of drugs designed for other targets but which were inhibiting also these enzymes).
References
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