Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives
A series of histamine bis-Schiff bases and bis-spinaceamine derivatives were synthesised and investigated as activators of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the membrane-associated hCA IV. All isoforms were effectively activated by the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2019.1630616 |
| _version_ | 1818533422376681472 |
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| author | Suleyman Akocak Nabih Lolak Silvia Bua Alessio Nocentini Claudiu T. Supuran |
| author_facet | Suleyman Akocak Nabih Lolak Silvia Bua Alessio Nocentini Claudiu T. Supuran |
| author_sort | Suleyman Akocak |
| collection | DOAJ |
| description | A series of histamine bis-Schiff bases and bis-spinaceamine derivatives were synthesised and investigated as activators of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the membrane-associated hCA IV. All isoforms were effectively activated by the new derivatives, with activation constants in the range of 4.73–10.2 µM for hCA I, 6.15–42.1 µM for hCA II, 2.37–32.7 µM for hCA IV and 32 nM–18.7 µM for hCA VII, respectively. The nature of the spacer between the two histamine/spinaceamine units of these molecules was the main contributor to the diverse activating efficacy, with a very different fine tuning for the diverse isoforms. As CA activators recently emerged as interesting agents for enhancing cognition, in the management of CA deficiencies, or for therapy memory and artificial tissues engineering, our compounds may be considered as candidates for such applications. |
| first_indexed | 2024-12-11T17:58:29Z |
| format | Article |
| id | doaj.art-c13a038da8794a79ac78bd0ea03efaf2 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-11T17:58:29Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-c13a038da8794a79ac78bd0ea03efaf22022-12-22T00:55:59ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-013411193119810.1080/14756366.2019.16306161630616Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivativesSuleyman Akocak0Nabih Lolak1Silvia Bua2Alessio Nocentini3Claudiu T. Supuran4Adiyaman UniversityAdiyaman UniversityUniversità degli Studi di FirenzeUniversità degli Studi di FirenzeUniversità degli Studi di FirenzeA series of histamine bis-Schiff bases and bis-spinaceamine derivatives were synthesised and investigated as activators of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic hCA I, II and VII, and the membrane-associated hCA IV. All isoforms were effectively activated by the new derivatives, with activation constants in the range of 4.73–10.2 µM for hCA I, 6.15–42.1 µM for hCA II, 2.37–32.7 µM for hCA IV and 32 nM–18.7 µM for hCA VII, respectively. The nature of the spacer between the two histamine/spinaceamine units of these molecules was the main contributor to the diverse activating efficacy, with a very different fine tuning for the diverse isoforms. As CA activators recently emerged as interesting agents for enhancing cognition, in the management of CA deficiencies, or for therapy memory and artificial tissues engineering, our compounds may be considered as candidates for such applications.http://dx.doi.org/10.1080/14756366.2019.1630616carbonic anhydraseactivatorhistaminespinaceamineproton shuttle |
| spellingShingle | Suleyman Akocak Nabih Lolak Silvia Bua Alessio Nocentini Claudiu T. Supuran Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives Journal of Enzyme Inhibition and Medicinal Chemistry carbonic anhydrase activator histamine spinaceamine proton shuttle |
| title | Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives |
| title_full | Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives |
| title_fullStr | Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives |
| title_full_unstemmed | Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives |
| title_short | Activation of human α-carbonic anhydrase isoforms I, II, IV and VII with bis-histamine schiff bases and bis-spinaceamine substituted derivatives |
| title_sort | activation of human α carbonic anhydrase isoforms i ii iv and vii with bis histamine schiff bases and bis spinaceamine substituted derivatives |
| topic | carbonic anhydrase activator histamine spinaceamine proton shuttle |
| url | http://dx.doi.org/10.1080/14756366.2019.1630616 |
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