Academic Journal
Computational study of amino acid-transition metal complexes as potential Helicobacter pylori urease enzyme inhibitors: DFT, molecular docking and ADMET analysis.
| Τίτλος: | Computational study of amino acid-transition metal complexes as potential Helicobacter pylori urease enzyme inhibitors: DFT, molecular docking and ADMET analysis. |
|---|---|
| Συγγραφείς: | Abdullahi, Muhammad Mustapha, Abdulsalam, Safiya, Hamza, Sa'adatu Auwal, Imam, Madina |
| Πηγή: | Discover Chemistry; 7/21/2026, Vol. 3 Issue 1, p1-28, 28p |
| Θεματικοί όροι: | Amino acids, Enzyme inhibitors, Metal complexes, Transition metals, Helicobacter pylori, Pharmacokinetics, Urease, Molecular docking, Density functional theory, Toxicity testing, Pharmaceutical chemistry |
| Περίληψη: | Helicobacter pylori urease is a nickel-dependent metalloenzyme that plays a critical role in bacterial survival and colonization within the acidic gastric environment, making it an attractive therapeutic target. In this study, the inhibitory potential of selected amino acids (serine, valine, and histidine) and their Cu(II), Ni(II), and Zn(II) complexes against H. pylori urease was investigated using density functional theory (DFT), molecular docking, drug-likeness evaluation, ADMET prediction, and toxicity assessment. Histidine was selected because of its metal-binding imidazole side chain, while serine and valine were chosen as representative amino acids possessing distinct coordination and physicochemical properties. Copper, nickel, and zinc were investigated due to their biological relevance and ability to modulate ligand–enzyme interactions through metal complexation. Molecular docking results revealed that metal coordination significantly enhanced binding affinity relative to the free amino acids. Among all investigated compounds, Cu(his)₂ exhibited the most favourable MolDock score (− 116.28 kcal/mol), followed by Zn(his)₂ (− 110.91 kcal/mol) and Ni(his)₂ (− 108.74 kcal/mol), with extensive hydrogen-bonding and hydrophobic interactions observed within the urease active site. Drug-likeness analysis indicated that all compounds satisfied Lipinski's Rule of Five without violations and possessed acceptable bioavailability characteristics. ADMET predictions suggested favourable metabolic profiles with minimal cytochrome P450 inhibition, while toxicity assessment indicated low toxicity for the free amino acids and moderate toxicity for several metal complexes, particularly copper-containing derivatives. Frontier molecular orbital analysis further demonstrated that metal complexation altered electronic properties and generally enhanced molecular reactivity. These computational findings suggest that histidine-based transition-metal complexes, particularly Cu(his)₂, warrant further investigation as potential urease-targeting agents. However, experimental validation through in vitro and in vivo studies is required to confirm their efficacy and safety. [ABSTRACT FROM AUTHOR] |
| Copyright of Discover Chemistry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Βάση Δεδομένων: | Complementary Index |
| FullText | Text: Availability: 0 |
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| Header | DbId: edb DbLabel: Complementary Index An: 195524173 RelevancyScore: 1082 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 1082.42236328125 |
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| Items | – Name: Title Label: Title Group: Ti Data: Computational study of amino acid-transition metal complexes as potential Helicobacter pylori urease enzyme inhibitors: DFT, molecular docking and ADMET analysis. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Abdullahi%2C+Muhammad+Mustapha%22">Abdullahi, Muhammad Mustapha</searchLink><br /><searchLink fieldCode="AR" term="%22Abdulsalam%2C+Safiya%22">Abdulsalam, Safiya</searchLink><br /><searchLink fieldCode="AR" term="%22Hamza%2C+Sa'adatu+Auwal%22">Hamza, Sa'adatu Auwal</searchLink><br /><searchLink fieldCode="AR" term="%22Imam%2C+Madina%22">Imam, Madina</searchLink> – Name: TitleSource Label: Source Group: Src Data: Discover Chemistry; 7/21/2026, Vol. 3 Issue 1, p1-28, 28p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Amino+acids%22">Amino acids</searchLink><br /><searchLink fieldCode="DE" term="%22Enzyme+inhibitors%22">Enzyme inhibitors</searchLink><br /><searchLink fieldCode="DE" term="%22Metal+complexes%22">Metal complexes</searchLink><br /><searchLink fieldCode="DE" term="%22Transition+metals%22">Transition metals</searchLink><br /><searchLink fieldCode="DE" term="%22Helicobacter+pylori%22">Helicobacter pylori</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacokinetics%22">Pharmacokinetics</searchLink><br /><searchLink fieldCode="DE" term="%22Urease%22">Urease</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+docking%22">Molecular docking</searchLink><br /><searchLink fieldCode="DE" term="%22Density+functional+theory%22">Density functional theory</searchLink><br /><searchLink fieldCode="DE" term="%22Toxicity+testing%22">Toxicity testing</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmaceutical+chemistry%22">Pharmaceutical chemistry</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Helicobacter pylori urease is a nickel-dependent metalloenzyme that plays a critical role in bacterial survival and colonization within the acidic gastric environment, making it an attractive therapeutic target. In this study, the inhibitory potential of selected amino acids (serine, valine, and histidine) and their Cu(II), Ni(II), and Zn(II) complexes against H. pylori urease was investigated using density functional theory (DFT), molecular docking, drug-likeness evaluation, ADMET prediction, and toxicity assessment. Histidine was selected because of its metal-binding imidazole side chain, while serine and valine were chosen as representative amino acids possessing distinct coordination and physicochemical properties. Copper, nickel, and zinc were investigated due to their biological relevance and ability to modulate ligand–enzyme interactions through metal complexation. Molecular docking results revealed that metal coordination significantly enhanced binding affinity relative to the free amino acids. Among all investigated compounds, Cu(his)₂ exhibited the most favourable MolDock score (− 116.28 kcal/mol), followed by Zn(his)₂ (− 110.91 kcal/mol) and Ni(his)₂ (− 108.74 kcal/mol), with extensive hydrogen-bonding and hydrophobic interactions observed within the urease active site. Drug-likeness analysis indicated that all compounds satisfied Lipinski's Rule of Five without violations and possessed acceptable bioavailability characteristics. ADMET predictions suggested favourable metabolic profiles with minimal cytochrome P450 inhibition, while toxicity assessment indicated low toxicity for the free amino acids and moderate toxicity for several metal complexes, particularly copper-containing derivatives. Frontier molecular orbital analysis further demonstrated that metal complexation altered electronic properties and generally enhanced molecular reactivity. These computational findings suggest that histidine-based transition-metal complexes, particularly Cu(his)₂, warrant further investigation as potential urease-targeting agents. However, experimental validation through in vitro and in vivo studies is required to confirm their efficacy and safety. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Discover Chemistry is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s44371-026-00862-8 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 28 StartPage: 1 Subjects: – SubjectFull: Amino acids Type: general – SubjectFull: Enzyme inhibitors Type: general – SubjectFull: Metal complexes Type: general – SubjectFull: Transition metals Type: general – SubjectFull: Helicobacter pylori Type: general – SubjectFull: Pharmacokinetics Type: general – SubjectFull: Urease Type: general – SubjectFull: Molecular docking Type: general – SubjectFull: Density functional theory Type: general – SubjectFull: Toxicity testing Type: general – SubjectFull: Pharmaceutical chemistry Type: general Titles: – TitleFull: Computational study of amino acid-transition metal complexes as potential Helicobacter pylori urease enzyme inhibitors: DFT, molecular docking and ADMET analysis. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Abdullahi, Muhammad Mustapha – PersonEntity: Name: NameFull: Abdulsalam, Safiya – PersonEntity: Name: NameFull: Hamza, Sa'adatu Auwal – PersonEntity: Name: NameFull: Imam, Madina IsPartOfRelationships: – BibEntity: Dates: – D: 21 M: 07 Text: 7/21/2026 Type: published Y: 2026 Numbering: – Type: volume Value: 3 – Type: issue Value: 1 Titles: – TitleFull: Discover Chemistry Type: main |
| ResultId | 1 |