Partial syntheses of aromatic amides : their anti-urease potential and docking studies
The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 μM compared to thiourea used as standard (21.5 ± 0.47 μM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Journal of biomolecular structure & dynamics - (2023) vom: 03. Okt., Seite 1-12 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Onocha, Patricia Akpomedaye [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-urease activity |
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| Anmerkungen: |
Date Revised 03.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1080/07391102.2023.2263876 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362813795 |
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| 100 | 1 | |a Onocha, Patricia Akpomedaye |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Partial syntheses of aromatic amides |b their anti-urease potential and docking studies |
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| 500 | |a Citation Status Publisher | ||
| 520 | |a The aromatic amide: N-p-trans-coumaroyltyramine (1) was isolated for the first time from the stem bark of Celtis zenkeri (Ulmaceae). Its four new derivatives (1a-d) and previously reported diacetylated product (1e) have been synthesized and characterized spectroscopically followed by their in vitro screening for anti-urease potential. The diacetylated product (1e) was found to be the most potent inhibitor with an IC50 value of 19.5 ± 0.23 μM compared to thiourea used as standard (21.5 ± 0.47 μM). Furthermore, molecular docking studies were conducted revealing striking interactions of the active compounds with catalytically important residues such as His593, Ala636 and Asp633. Subsequently, the prime MM-GBSA calculations provided the ligand binding and strain energies. The molecular dynamic simulations validated the docked and post-docked complexes where compounds 1b, 1c, 1d and 1e remained stable throughout the simulation. This study provides insight into the N-p-trans-coumaroyltyramine derivatives (1b-e) that can block the substrate entry, thereby inhibiting the urease's catalytic activity. Hence, these hit compounds can proceed for further pre-clinical studies for drug discovery against urease.Communicated by Ramaswamy H. Sarma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Celtis zenkeri | |
| 650 | 4 | |a N-p-trans-coumaroyltyramine | |
| 650 | 4 | |a anti-urease activity | |
| 650 | 4 | |a aromatic amide derivatives | |
| 650 | 4 | |a molecular docking | |
| 700 | 1 | |a Okpala, Ejike Onwudiegwu |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Muhammad Shaiq |e verfasserin |4 aut | |
| 700 | 1 | |a Rahman, Noor |e verfasserin |4 aut | |
| 700 | 1 | |a Zafar, Humaira |e verfasserin |4 aut | |
| 700 | 1 | |a Oloyede, Ganiyat Kehinde |e verfasserin |4 aut | |
| 700 | 1 | |a Nwozo, Sarah Oyenibe |e verfasserin |4 aut | |
| 700 | 1 | |a Lateef, Mehreen |e verfasserin |4 aut | |
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