Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy
Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the...
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MDPI AG
2022-06-01
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| Series: | Current Issues in Molecular Biology |
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| author | Mohd Saeed Munazzah Tasleem Ambreen Shoib Mohd Adnan Kausar Abdel Moneim E. Sulieman Nadiyah M. Alabdallah Zeina El Asmar Abdelmuhsin Abdelgadir Asma Al-Shammary Md Jahoor Alam Riadh Badroui Maryam Zahin |
| author_facet | Mohd Saeed Munazzah Tasleem Ambreen Shoib Mohd Adnan Kausar Abdel Moneim E. Sulieman Nadiyah M. Alabdallah Zeina El Asmar Abdelmuhsin Abdelgadir Asma Al-Shammary Md Jahoor Alam Riadh Badroui Maryam Zahin |
| author_sort | Mohd Saeed |
| collection | DOAJ |
| description | Diabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBE<sub>DB</sub> database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors. |
| first_indexed | 2024-03-09T12:04:57Z |
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| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-09T12:04:57Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj.art-a6c6aa5152e84ddd82428611916a83ae2023-11-30T22:59:28ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-06-014472825284110.3390/cimb44070194Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral NeuropathyMohd Saeed0Munazzah Tasleem1Ambreen Shoib2Mohd Adnan Kausar3Abdel Moneim E. Sulieman4Nadiyah M. Alabdallah5Zeina El Asmar6Abdelmuhsin Abdelgadir7Asma Al-Shammary8Md Jahoor Alam9Riadh Badroui10Maryam Zahin11Department of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaSchool of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu 610054, ChinaDepartment of Clinical Pharmacy, College of Pharmacy, Jazan University, P.O. Box 114, Jazan 45142, Saudi ArabiaDepartment of Biochemistry, College of Medicine, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Biology, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi ArabiaDepartment of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Public Health, College of Public Health and Health Informatics, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaDepartment of Biology, College of Sciences, University of Ha’il, P.O. Box 2240, Ha’il 81451, Saudi ArabiaJames Graham Brown Cancer Center, University of Louisville, Louisville, KY 4020, USADiabetic peripheral neuropathy (DPN) is a common diabetes complication (DM). Aldose reductase -2 (ALR-2) is an oxidoreductase enzyme that is most extensively studied therapeutic target for diabetes-related complications that can be inhibited by epalrestat, which has severe adverse effects; hence the discovery of potent natural inhibitors is desired. In response, a pharmacophore model based on the properties of eplarestat was generated. The specified pharmacophore model searched the NuBBE<sub>DB</sub> database of natural compounds for prospective lead candidates. To assess the drug-likeness and ADMET profile of the compounds, a series of in silico filtering procedures were applied. The compounds were then put through molecular docking and interaction analysis. In comparison to the reference drug, four compounds showed increased binding affinity and demonstrated critical residue interactions with greater stability and specificity. As a result, we have identified four potent inhibitors: ZINC000002895847, ZINC000002566593, ZINC000012447255, and ZINC000065074786, that could be used as pharmacological niches to develop novel ALR-2 inhibitors.https://www.mdpi.com/1467-3045/44/7/194pharmacophorestructure-based drug designNuBBE<sub>DB</sub>ADMETmolecular docking |
| spellingShingle | Mohd Saeed Munazzah Tasleem Ambreen Shoib Mohd Adnan Kausar Abdel Moneim E. Sulieman Nadiyah M. Alabdallah Zeina El Asmar Abdelmuhsin Abdelgadir Asma Al-Shammary Md Jahoor Alam Riadh Badroui Maryam Zahin Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy Current Issues in Molecular Biology pharmacophore structure-based drug design NuBBE<sub>DB</sub> ADMET molecular docking |
| title | Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy |
| title_full | Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy |
| title_fullStr | Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy |
| title_full_unstemmed | Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy |
| title_short | Identification of Putative Plant-Based ALR-2 Inhibitors to Treat Diabetic Peripheral Neuropathy |
| title_sort | identification of putative plant based alr 2 inhibitors to treat diabetic peripheral neuropathy |
| topic | pharmacophore structure-based drug design NuBBE<sub>DB</sub> ADMET molecular docking |
| url | https://www.mdpi.com/1467-3045/44/7/194 |
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