Novel 2-substituted-benzimidazole-6-sulfonamides as carbonic anhydrase inhibitors : synthesis, biological evaluation against isoforms I, II, IX and XII and molecular docking studies
Inhibition of Carbonic Anhydrases (CAs) has been clinically exploited for many decades for a variety of therapeutic applications. Within a research project aimed at developing novel classes of CA inhibitors (CAIs) with a proper selectivity for certain isoforms, a series of derivatives featuring the 2-substituted-benzimidazole-6-sulfonamide scaffold, conceived as frozen analogs of Schiff bases and secondary amines previously reported in the literature as CAIs, were investigated. Enzyme inhibition assays on physiologically relevant human CA I, II, IX and XII isoforms revealed a number of potent CAIs, showing promising selectivity profiles towards the transmembrane tumor-associated CA IX and XII enzymes. Computational studies were attained to clarify the structural determinants behind the activities and selectivity profiles of the novel inhibitors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 34(2019), 1 vom: 02. Dez., Seite 1697-1710 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Milite, Ciro [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.12.2019 Date Revised 23.12.2019 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2019.1666836 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM30145177X |
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| 245 | 1 | 0 | |a Novel 2-substituted-benzimidazole-6-sulfonamides as carbonic anhydrase inhibitors |b synthesis, biological evaluation against isoforms I, II, IX and XII and molecular docking studies |
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| 500 | |a Date Completed 23.12.2019 | ||
| 500 | |a Date Revised 23.12.2019 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Inhibition of Carbonic Anhydrases (CAs) has been clinically exploited for many decades for a variety of therapeutic applications. Within a research project aimed at developing novel classes of CA inhibitors (CAIs) with a proper selectivity for certain isoforms, a series of derivatives featuring the 2-substituted-benzimidazole-6-sulfonamide scaffold, conceived as frozen analogs of Schiff bases and secondary amines previously reported in the literature as CAIs, were investigated. Enzyme inhibition assays on physiologically relevant human CA I, II, IX and XII isoforms revealed a number of potent CAIs, showing promising selectivity profiles towards the transmembrane tumor-associated CA IX and XII enzymes. Computational studies were attained to clarify the structural determinants behind the activities and selectivity profiles of the novel inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Carbonic anhydrase inhibitors | |
| 650 | 4 | |a benzimidazole-sulfonamides | |
| 650 | 4 | |a isoform-selective inhibitors | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a reduced flexibility approach | |
| 650 | 7 | |a Amines |2 NLM | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a CA11 protein, human |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |2 NLM | |
| 650 | 7 | |a Isoenzymes |2 NLM | |
| 650 | 7 | |a Nerve Tissue Proteins |2 NLM | |
| 650 | 7 | |a Schiff Bases |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase I |2 NLM | |
| 650 | 7 | |a EC 4.2.1.- |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase II |2 NLM | |
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| 650 | 7 | |a CA1 carbonic anhydrase, human |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a CA2 protein, human |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 | |
| 700 | 1 | |a Amendola, Giorgio |e verfasserin |4 aut | |
| 700 | 1 | |a Nocentini, Alessio |e verfasserin |4 aut | |
| 700 | 1 | |a Bua, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Cipriano, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Barresi, Elisabetta |e verfasserin |4 aut | |
| 700 | 1 | |a Feoli, Alessandra |e verfasserin |4 aut | |
| 700 | 1 | |a Novellino, Ettore |e verfasserin |4 aut | |
| 700 | 1 | |a Da Settimo, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 700 | 1 | |a Castellano, Sabrina |e verfasserin |4 aut | |
| 700 | 1 | |a Cosconati, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Taliani, Sabrina |e verfasserin |4 aut | |
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