Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII. The out of the active site pocket for the design of selective inhibitors?
New C-glycosides and α,β-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 36(2021), 1 vom: 05. Dez., Seite 2118-2127 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Riafrecha, Leonardo E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2022 Date Revised 26.01.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2021.1982933 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM331487829 |
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| 100 | 1 | |a Riafrecha, Leonardo E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Vanillin enones as selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII. The out of the active site pocket for the design of selective inhibitors? |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 26.01.2022 | ||
| 500 | |a Date Revised 26.01.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a New C-glycosides and α,β-unsaturated ketones incorporating the 4-hydroxy-3-methoxyphenyl (vanillin) moiety as inhibitors of carbonic anhydrase (CA, EC 4.2.1.1) isoforms have been investigated. The inhibition profile of these compounds is presented against four human CA (hCA) isozymes, comprising hCAs I and II (cytosolic, ubiquitous enzymes) and hCAs IX and XII (tumour associated isozymes). Docking analysis of the inhibitors within the active sites of these enzymes has been performed and is discussed, showing that the observed selectivity could be explained in terms of an alternative pocket out of the CA active site where some of these compounds may bind. Several derivatives were identified as selective inhibitors of the tumour-associated hCA IX and XII. Their discovery might be a step in the strategy for finding an effective non-sulfonamide CA inhibitor useful in therapy/diagnosis of hypoxic tumours or other pathologies in which CA isoforms are involved | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Vanillin | |
| 650 | 4 | |a carbonic anhydrase | |
| 650 | 4 | |a enones | |
| 650 | 4 | |a enzyme inhibitors | |
| 650 | 4 | |a molecular docking | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Benzaldehydes |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |2 NLM | |
| 650 | 7 | |a vanillin |2 NLM | |
| 650 | 7 | |a CHI530446X |2 NLM | |
| 650 | 7 | |a CA9 protein, human |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase IX |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrases |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a carbonic anhydrase XII |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 700 | 1 | |a Le Pors, Macarena S |e verfasserin |4 aut | |
| 700 | 1 | |a Lavecchia, Martín J |e verfasserin |4 aut | |
| 700 | 1 | |a Bua, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 700 | 1 | |a Colinas, Pedro A |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/14756366.2021.1982933 |3 Volltext |
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