Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase
Inorganic anions inhibit the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) generally by coordinating to the active site metal ion. Cyanate was reported as a non-coordinating CA inhibitor but those erroneous results were subsequently corrected by another group. We review the anion CA inhibitors (...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1882453 |
| _version_ | 1818954320698146816 |
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| author | Alessio Nocentini Andrea Angeli Fabrizio Carta Jean-Yves Winum Raivis Zalubovskis Simone Carradori Clemente Capasso William A. Donald Claudiu T. Supuran |
| author_facet | Alessio Nocentini Andrea Angeli Fabrizio Carta Jean-Yves Winum Raivis Zalubovskis Simone Carradori Clemente Capasso William A. Donald Claudiu T. Supuran |
| author_sort | Alessio Nocentini |
| collection | DOAJ |
| description | Inorganic anions inhibit the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) generally by coordinating to the active site metal ion. Cyanate was reported as a non-coordinating CA inhibitor but those erroneous results were subsequently corrected by another group. We review the anion CA inhibitors (CAIs) in the more general context of drug design studies and the discovery of a large number of inhibitor classes and inhibition mechanisms, including zinc binders (sulphonamides and isosteres, dithiocabamates and isosteres, thiols, selenols, benzoxaboroles, ninhydrins, etc.); inhibitors anchoring to the zinc-coordinated water molecule (phenols, polyamines, sulfocoumarins, thioxocoumarins, catechols); CAIs occluding the entrance to the active site (coumarins and derivatives, lacosamide), as well as compounds that bind outside the active site. All these new chemotypes integrated with a general procedure for obtaining isoform-selective compounds (the tail approach) has resulted, through the guidance of rigorous X-ray crystallography experiments, in the development of highly selective CAIs for all human CA isoforms with many pharmacological applications. |
| first_indexed | 2024-12-20T10:20:18Z |
| format | Article |
| id | doaj.art-c312ff071beb4ce3a541ee3fd2098cc5 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-20T10:20:18Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c312ff071beb4ce3a541ee3fd2098cc52022-12-21T19:43:56ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136156158010.1080/14756366.2021.18824531882453Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydraseAlessio Nocentini0Andrea Angeli1Fabrizio Carta2Jean-Yves Winum3Raivis Zalubovskis4Simone Carradori5Clemente Capasso6William A. Donald7Claudiu T. Supuran8Neurofarba Department, Pharmaceutical and Nutraceutical Section, University of FlorenceNeurofarba Department, Pharmaceutical and Nutraceutical Section, University of FlorenceNeurofarba Department, Pharmaceutical and Nutraceutical Section, University of FlorenceIBMM, Univ. Montpellier, CNRS, ENSCMLatvian Institute of Organic SynthesisDepartment of Pharmacy, "G. d'Annunzio" University of Chieti-PescaraInstitute of Biosciences and Bioresources, National Research CouncilSchool of Chemistry, University of New South WalesNeurofarba Department, Pharmaceutical and Nutraceutical Section, University of FlorenceInorganic anions inhibit the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) generally by coordinating to the active site metal ion. Cyanate was reported as a non-coordinating CA inhibitor but those erroneous results were subsequently corrected by another group. We review the anion CA inhibitors (CAIs) in the more general context of drug design studies and the discovery of a large number of inhibitor classes and inhibition mechanisms, including zinc binders (sulphonamides and isosteres, dithiocabamates and isosteres, thiols, selenols, benzoxaboroles, ninhydrins, etc.); inhibitors anchoring to the zinc-coordinated water molecule (phenols, polyamines, sulfocoumarins, thioxocoumarins, catechols); CAIs occluding the entrance to the active site (coumarins and derivatives, lacosamide), as well as compounds that bind outside the active site. All these new chemotypes integrated with a general procedure for obtaining isoform-selective compounds (the tail approach) has resulted, through the guidance of rigorous X-ray crystallography experiments, in the development of highly selective CAIs for all human CA isoforms with many pharmacological applications.http://dx.doi.org/10.1080/14756366.2021.1882453carbonic anhydraseinhibitorsulphonamideinhibition mechanismscyanate |
| spellingShingle | Alessio Nocentini Andrea Angeli Fabrizio Carta Jean-Yves Winum Raivis Zalubovskis Simone Carradori Clemente Capasso William A. Donald Claudiu T. Supuran Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase Journal of Enzyme Inhibition and Medicinal Chemistry carbonic anhydrase inhibitor sulphonamide inhibition mechanisms cyanate |
| title | Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| title_full | Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| title_fullStr | Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| title_full_unstemmed | Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| title_short | Reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| title_sort | reconsidering anion inhibitors in the general context of drug design studies of modulators of activity of the classical enzyme carbonic anhydrase |
| topic | carbonic anhydrase inhibitor sulphonamide inhibition mechanisms cyanate |
| url | http://dx.doi.org/10.1080/14756366.2021.1882453 |
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