Novel 3-substituted coumarins as selective human carbonic anhydrase IX and XII inhibitors : Synthesis, biological and molecular dynamics analysis
Copyright © 2020 Elsevier Masson SAS. All rights reserved..
In this study, diverse series of coumarin derivatives were developed as potential carbonic anhydrase inhibitors (CAIs). A "tail" approach was adopted by selecting the coumarin motif as a tail that is connected to the ZBG benzenesulfonamide moiety via a hydrazine (4a,b) or hydrazide (5a,b) linker. Thereafter, an aryl sulfone tail was incorporated to afford the dual tailed coumarin-sulfonamide arylsulfonehydrazones (13a-d) and hydrazides (14a,b). Then, the ZBG were removed from compounds 13 and 14 to furnish coumarin arylsulfonehydrazones (11a-d) and hydrazides (12a,b). Coumarin-sulfonamides 4 and 5 emerged as non-selective CAIs as they displayed good inhibitory activities toward all the examined CA isozymes (I, II, IX and XII) in the nanomolar ranges. Interestingly, the "dual-tail" approach (compounds 13 and 14) succeeded in achieving a good activity and selectivity toward CA IX/XII over the physiologically dominant CA I/II. In particular, compounds 13d and 14a were the most selective coumarin-sulfonamide counterparts. Concerning non-sulfonamide coumarin derivatives, coumarins 8 exhibited excellent activity and selectivity profiles against the target hCA IX/XII, whereas, coumarins 11 and 12 reported excellent selectivity profile, but they barely inhibited hCA IX/XII with KIs spanning in the micromolar ranges. Furthermore, molecular modelling studies were applied to get a deep focus about the feasible affinities and binding interactions for target coumarin-sulfonamides 4, 5, 13 and 14 with the active site for CA II, IX and XII isoforms.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:209 |
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| Enthalten in: |
European journal of medicinal chemistry - 209(2021) vom: 01. Jan., Seite 112897 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdelrahman, Mohamed A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.04.2021 Date Revised 21.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejmech.2020.112897 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316086959 |
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| 100 | 1 | |a Abdelrahman, Mohamed A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel 3-substituted coumarins as selective human carbonic anhydrase IX and XII inhibitors |b Synthesis, biological and molecular dynamics analysis |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 21.04.2021 | ||
| 500 | |a Date Revised 21.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier Masson SAS. All rights reserved. | ||
| 520 | |a In this study, diverse series of coumarin derivatives were developed as potential carbonic anhydrase inhibitors (CAIs). A "tail" approach was adopted by selecting the coumarin motif as a tail that is connected to the ZBG benzenesulfonamide moiety via a hydrazine (4a,b) or hydrazide (5a,b) linker. Thereafter, an aryl sulfone tail was incorporated to afford the dual tailed coumarin-sulfonamide arylsulfonehydrazones (13a-d) and hydrazides (14a,b). Then, the ZBG were removed from compounds 13 and 14 to furnish coumarin arylsulfonehydrazones (11a-d) and hydrazides (12a,b). Coumarin-sulfonamides 4 and 5 emerged as non-selective CAIs as they displayed good inhibitory activities toward all the examined CA isozymes (I, II, IX and XII) in the nanomolar ranges. Interestingly, the "dual-tail" approach (compounds 13 and 14) succeeded in achieving a good activity and selectivity toward CA IX/XII over the physiologically dominant CA I/II. In particular, compounds 13d and 14a were the most selective coumarin-sulfonamide counterparts. Concerning non-sulfonamide coumarin derivatives, coumarins 8 exhibited excellent activity and selectivity profiles against the target hCA IX/XII, whereas, coumarins 11 and 12 reported excellent selectivity profile, but they barely inhibited hCA IX/XII with KIs spanning in the micromolar ranges. Furthermore, molecular modelling studies were applied to get a deep focus about the feasible affinities and binding interactions for target coumarin-sulfonamides 4, 5, 13 and 14 with the active site for CA II, IX and XII isoforms | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Carbonic anhydrase inhibitors | |
| 650 | 4 | |a Coumarins | |
| 650 | 4 | |a Molecular dynamics | |
| 650 | 4 | |a Sulfonamides | |
| 650 | 4 | |a Tail approach | |
| 650 | 7 | |a Antigens, Neoplasm |2 NLM | |
| 650 | 7 | |a Carbonic Anhydrase Inhibitors |2 NLM | |
| 650 | 7 | |a Coumarins |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 Ibrahim, Hany S |e verfasserin |4 aut | |
| 700 | 1 | |a Nocentini, Alessio |e verfasserin |4 aut | |
| 700 | 1 | |a Eldehna, Wagdy M |e verfasserin |4 aut | |
| 700 | 1 | |a Bonardi, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Abdel-Aziz, Hatem A |e verfasserin |4 aut | |
| 700 | 1 | |a Gratteri, Paola |e verfasserin |4 aut | |
| 700 | 1 | |a Abou-Seri, Sahar M |e verfasserin |4 aut | |
| 700 | 1 | |a Supuran, Claudiu T |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of medicinal chemistry |d 1994 |g 209(2021) vom: 01. Jan., Seite 112897 |w (DE-627)NLM106608835 |x 1768-3254 |7 nnns |
| 773 | 1 | 8 | |g volume:209 |g year:2021 |g day:01 |g month:01 |g pages:112897 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejmech.2020.112897 |3 Volltext |
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