Keto-bridged dual triazole-linked benzenesulfonamides as potent carbonic anhydrase and cathepsin B inhibitors
Background: Inhibition of human carbonic anhydrase (hCA) isoforms IX and XII with concurrent inhibition of cathepsin B is a promising approach for targeting cancers. Methods/results: 28 keto-bridged dual triazole-containing benzenesulfonamides were synthesized and tested, following the multitarget approach, for their efficacy as inhibitors of cathepsin B and hCA isoforms (I, II, IX, XII). The synthesized compounds showed excellent inhibition of CA isoforms (IX and XII) and cathepsin B. Compound 8i exhibited better and more selective inhibition of the cancer-associated isoform hCA IX as compared with acetazolamide (reference drug) and SLC-0111 (potent lead as carbonic anhydrase inhibitor). Molecular docking studies were also carried out. Conclusion: The present work gives important generalizations for the development of isoform-selective hCA inhibitors endowed with anti-cathepsin properties.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 20 vom: 01. Okt., Seite 1843-1863 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vats, Lalit [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.11.2023 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0201 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363695206 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: Inhibition of human carbonic anhydrase (hCA) isoforms IX and XII with concurrent inhibition of cathepsin B is a promising approach for targeting cancers. Methods/results: 28 keto-bridged dual triazole-containing benzenesulfonamides were synthesized and tested, following the multitarget approach, for their efficacy as inhibitors of cathepsin B and hCA isoforms (I, II, IX, XII). The synthesized compounds showed excellent inhibition of CA isoforms (IX and XII) and cathepsin B. Compound 8i exhibited better and more selective inhibition of the cancer-associated isoform hCA IX as compared with acetazolamide (reference drug) and SLC-0111 (potent lead as carbonic anhydrase inhibitor). Molecular docking studies were also carried out. Conclusion: The present work gives important generalizations for the development of isoform-selective hCA inhibitors endowed with anti-cathepsin properties | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SLC-0111 | |
| 650 | 4 | |a anticancer agents | |
| 650 | 4 | |a carbonic anhydrase inhibitor | |
| 650 | 4 | |a cathepsin B inhibitor | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a tail approach | |
| 650 | 7 | |a Carbonic Anhydrases |2 NLM | |
| 650 | 7 | |a EC 4.2.1.1 |2 NLM | |
| 650 | 7 | |a Triazoles |2 NLM | |
| 650 | 7 | |a Cathepsin B |2 NLM | |
| 650 | 7 | |a EC 3.4.22.1 |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |2 NLM | |
| 650 | 7 | |a Protein Isoforms |2 NLM | |
| 700 | 1 | |a Arya, Priyanka |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Rajiv |e verfasserin |4 aut | |
| 700 | 1 | |a Giovannuzzi, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Raghav, Neera |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Pawan K |e verfasserin |4 aut | |
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