Design and synthesis of some new benzoylthioureido benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors
The present investigation reports the design and synthesis of three series of benzoylthioureido derivatives bearing either benzenesulfonamide 7a-f, benzoic acid 8a-f or ethylbenzoate 9a-f moieties. The synthesised compounds were screened for their carbonic anhydrase inhibitory activity (CAI) against four isoforms hCA I, II, IX, and XII. Compounds 7a, 7b, 7c, and 7f exhibited a potent inhibitory activity towards hCAI (Kis = 58.20, 56.30, 33.00, and 43.00 nM), respectively compared to acetazolamide (AAZ) and SLC-0111 (Kis = 250.00 and 5080.00 nM). Compounds 7a, 7b, 7c, 7e, and 7f elicited selectivity over h CA II (Kis = 2.50, 2.10, 56.60,39.60 and 39.00 nM) respectively, relative to AAZ and SLC-0111(Kis = 12.10 and 960.00 nM). Also, compounds 7c, 7f, and 9e displayed selectivity against the tumour-associated isoform hCA IX (Kis = 31.20, 30.00 and 29.00 nM) respectively, compared to AAZ and SLC-0111 (Kis = 25.70 and 45.00 nM). Additionally, compounds 8a and 8f revealed a moderate to superior selectivity towards hCAXII (Kis = 17.00 and 11.00 nM) relative to AAZ and SLC-0111(Kis = 5.70 and 45.00 nM). Molecular docking and ADME prediction studies were performed on the most active compounds to shed light on their interaction with the hot spots of the active site of CA isoforms, in addition to prediction of their pharmacokinetic and physicochemical properties.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 38(2023), 1 vom: 25. Dez., Seite 12-23 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Oudah, Khulood H [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.10.2022 Date Revised 13.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2022.2132485 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348196172 |
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| 041 | |a eng | ||
| 100 | 1 | |a Oudah, Khulood H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design and synthesis of some new benzoylthioureido benzenesulfonamide derivatives and their analogues as carbonic anhydrase inhibitors |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 31.10.2022 | ||
| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The present investigation reports the design and synthesis of three series of benzoylthioureido derivatives bearing either benzenesulfonamide 7a-f, benzoic acid 8a-f or ethylbenzoate 9a-f moieties. The synthesised compounds were screened for their carbonic anhydrase inhibitory activity (CAI) against four isoforms hCA I, II, IX, and XII. Compounds 7a, 7b, 7c, and 7f exhibited a potent inhibitory activity towards hCAI (Kis = 58.20, 56.30, 33.00, and 43.00 nM), respectively compared to acetazolamide (AAZ) and SLC-0111 (Kis = 250.00 and 5080.00 nM). Compounds 7a, 7b, 7c, 7e, and 7f elicited selectivity over h CA II (Kis = 2.50, 2.10, 56.60,39.60 and 39.00 nM) respectively, relative to AAZ and SLC-0111(Kis = 12.10 and 960.00 nM). Also, compounds 7c, 7f, and 9e displayed selectivity against the tumour-associated isoform hCA IX (Kis = 31.20, 30.00 and 29.00 nM) respectively, compared to AAZ and SLC-0111 (Kis = 25.70 and 45.00 nM). Additionally, compounds 8a and 8f revealed a moderate to superior selectivity towards hCAXII (Kis = 17.00 and 11.00 nM) relative to AAZ and SLC-0111(Kis = 5.70 and 45.00 nM). Molecular docking and ADME prediction studies were performed on the most active compounds to shed light on their interaction with the hot spots of the active site of CA isoforms, in addition to prediction of their pharmacokinetic and physicochemical properties | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Carbonic anhydrase | |
| 650 | 4 | |a SLC-0111 | |
| 650 | 4 | |a benzenesulfonamides | |
| 650 | 4 | |a zinc binding-group (ZBG) | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |2 NLM | |
| 650 | 7 | |a SLC-0111 |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrases |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a Acetazolamide |2 NLM | |
| 650 | 7 | |a O3FX965V0I |2 NLM | |
| 650 | 7 | |a Protein Isoforms |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase IX |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 700 | 1 | |a Mahmoud, Walaa R |e verfasserin |4 aut | |
| 700 | 1 | |a Awadallah, Fadi M |e verfasserin |4 aut | |
| 700 | 1 | |a Taher, Azza T |e verfasserin |4 aut | |
| 700 | 1 | |a Abbas, Safinaz E-S |e verfasserin |4 aut | |
| 700 | 1 | |a Allam, Heba Abdelrasheed |e verfasserin |4 aut | |
| 700 | 1 | |a Vullo, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of enzyme inhibition and medicinal chemistry |d 2002 |g 38(2023), 1 vom: 25. Dez., Seite 12-23 |w (DE-627)NLM121560376 |x 1475-6374 |7 nnns |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/14756366.2022.2132485 |3 Volltext |
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