Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1)
The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/10/1404 |
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| author | Zainab Bibi Irfa Asghar Naeem Mahmood Ashraf Iftikhar Zeb Umer Rashid Arslan Hamid Maria Kanwal Ali Ashraf Atef Hatamleh Munirah Abdullah Al-Dosary Raza Ahmad Muhammad Ali |
| author_facet | Zainab Bibi Irfa Asghar Naeem Mahmood Ashraf Iftikhar Zeb Umer Rashid Arslan Hamid Maria Kanwal Ali Ashraf Atef Hatamleh Munirah Abdullah Al-Dosary Raza Ahmad Muhammad Ali |
| author_sort | Zainab Bibi |
| collection | DOAJ |
| description | The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein–ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein–ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb–Schrödinger interaction energy, and Lennard–Jones–Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance. |
| first_indexed | 2024-03-10T20:58:18Z |
| format | Article |
| id | doaj.art-058a2d83277f4032a33cdf3c22b3e305 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:58:18Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-058a2d83277f4032a33cdf3c22b3e3052023-11-19T17:42:01ZengMDPI AGPharmaceuticals1424-82472023-10-011610140410.3390/ph16101404Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1)Zainab Bibi0Irfa Asghar1Naeem Mahmood Ashraf2Iftikhar Zeb3Umer Rashid4Arslan Hamid5Maria Kanwal Ali6Ashraf Atef Hatamleh7Munirah Abdullah Al-Dosary8Raza Ahmad9Muhammad Ali10Department of Biotechnology, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Biotechnology, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanSchool of Biochemistry and Biotechnology, University of Punjab, Lahore P.O. Box 54590, PakistanDepartment of Biotechnology, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Chemistry, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanLIMES Institute, University of Bonn, D-53113 Bonn, GermanyInstitute of Nuclear Medicine, Oncology and Radiotherapy (INOR), Abbottabad 22060, PakistanDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Biotechnology, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanDepartment of Biotechnology, Abbottabad Campus, COMSATS University Islamabad, Abbottabad 22060, PakistanThe effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein–ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein–ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb–Schrödinger interaction energy, and Lennard–Jones–Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance.https://www.mdpi.com/1424-8247/16/10/1404New Delhi metallo β-lactamase-1phytochemicalspolyphenolsmolecular dynamics simulationsmetallo β-lactamase inhibitors |
| spellingShingle | Zainab Bibi Irfa Asghar Naeem Mahmood Ashraf Iftikhar Zeb Umer Rashid Arslan Hamid Maria Kanwal Ali Ashraf Atef Hatamleh Munirah Abdullah Al-Dosary Raza Ahmad Muhammad Ali Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) Pharmaceuticals New Delhi metallo β-lactamase-1 phytochemicals polyphenols molecular dynamics simulations metallo β-lactamase inhibitors |
| title | Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) |
| title_full | Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) |
| title_fullStr | Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) |
| title_full_unstemmed | Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) |
| title_short | Prediction of Phytochemicals for Their Potential to Inhibit New Delhi Metallo β-Lactamase (NDM-1) |
| title_sort | prediction of phytochemicals for their potential to inhibit new delhi metallo β lactamase ndm 1 |
| topic | New Delhi metallo β-lactamase-1 phytochemicals polyphenols molecular dynamics simulations metallo β-lactamase inhibitors |
| url | https://www.mdpi.com/1424-8247/16/10/1404 |
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