Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms
Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1512597 |
| _version_ | 1828894008703713280 |
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| author | Alessio Nocentini Alessandro Bonardi Paola Gratteri Bruno Cerra Antimo Gioiello Claudiu T. Supuran |
| author_facet | Alessio Nocentini Alessandro Bonardi Paola Gratteri Bruno Cerra Antimo Gioiello Claudiu T. Supuran |
| author_sort | Alessio Nocentini |
| collection | DOAJ |
| description | Bile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a wealth of steroids against four relevant hCA isoforms. Steroids displaying pendants and functional groups of the carboxylate, phenolic or sulfonate types appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9–89.9 µM). Docking studies displayed the different chemotypes CA inhibition mechanisms. Molecular dynamics (MD) gave insights on the stability over time of hyocholic acid binding to CA II. |
| first_indexed | 2024-12-13T14:04:02Z |
| format | Article |
| id | doaj.art-c4da7939832b4fa48310ee9d70017d17 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T14:04:02Z |
| publishDate | 2018-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c4da7939832b4fa48310ee9d70017d172022-12-21T23:42:39ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742018-01-013311453145910.1080/14756366.2018.15125971512597Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanismsAlessio Nocentini0Alessandro Bonardi1Paola Gratteri2Bruno Cerra3Antimo Gioiello4Claudiu T. Supuran5University of FirenzeUniversity of FirenzeUniversity of FirenzeUniversity of PerugiaUniversity of PerugiaUniversity of FlorenceBile acids have been shown to inhibit human (h) carbonic anhydrases (CA, EC 4.2.1.1) along the gastrointestinal tract, including hCA II. The elucidation of the hormonal inhibition mechanism of the bile acid cholate to hCA II was provided in 2014 by X-ray crystallography. Herein, we extend the inhibition study to a wealth of steroids against four relevant hCA isoforms. Steroids displaying pendants and functional groups of the carboxylate, phenolic or sulfonate types appended at the tetracyclic ring were shown to inhibit the cytosolic CA II and the tumor-associated, transmembrane CA IX in a medium micromolar range (38.9–89.9 µM). Docking studies displayed the different chemotypes CA inhibition mechanisms. Molecular dynamics (MD) gave insights on the stability over time of hyocholic acid binding to CA II.http://dx.doi.org/10.1080/14756366.2018.1512597Carbonic anhydraseinhibitorsteroidsphenolbile acid |
| spellingShingle | Alessio Nocentini Alessandro Bonardi Paola Gratteri Bruno Cerra Antimo Gioiello Claudiu T. Supuran Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms Journal of Enzyme Inhibition and Medicinal Chemistry Carbonic anhydrase inhibitor steroids phenol bile acid |
| title | Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| title_full | Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| title_fullStr | Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| title_full_unstemmed | Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| title_short | Steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| title_sort | steroids interfere with human carbonic anhydrase activity by using alternative binding mechanisms |
| topic | Carbonic anhydrase inhibitor steroids phenol bile acid |
| url | http://dx.doi.org/10.1080/14756366.2018.1512597 |
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