Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety
New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Journal of medicinal chemistry - 67(2024), 4 vom: 22. Feb., Seite 3018-3038 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Al-Matarneh, Cristina M [VerfasserIn] |
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| Links: |
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| Themen: |
Antigens, Neoplasm |
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| Anmerkungen: |
Date Completed 23.02.2024 Date Revised 28.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.3c02190 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367904217 |
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| 520 | |a New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |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 Protein Isoforms |2 NLM | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 700 | 1 | |a Pinteala, Mariana |e verfasserin |4 aut | |
| 700 | 1 | |a Nicolescu, Alina |e verfasserin |4 aut | |
| 700 | 1 | |a Silion, Mihaela |e verfasserin |4 aut | |
| 700 | 1 | |a Mocci, Francesca |e verfasserin |4 aut | |
| 700 | 1 | |a Puf, Razvan |e verfasserin |4 aut | |
| 700 | 1 | |a Angeli, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Ferraroni, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 700 | 1 | |a Zara, Susi |e verfasserin |4 aut | |
| 700 | 1 | |a Carradori, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Paoletti, Niccolò |e verfasserin |4 aut | |
| 700 | 1 | |a Bonardi, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Gratteri, Paola |e verfasserin |4 aut | |
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