A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents
Background: Diabetes mellitus is a long-standing and debilitating metabolic condition that imposes a substantial global health burden, leading to severe and widespread complications. Objectives: This study aims to predict physicochemical properties of 1,3,4-oxadiazole derivatives using in-silico met...
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Creative Pharma Assent
2025-04-01
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| Series: | Journal of Applied Pharmaceutical Research |
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| author | Mohini Patidar Raghvendra Dubey Sunita Minz Madhulika Pradhan Nitin Deshmukh |
| author_facet | Mohini Patidar Raghvendra Dubey Sunita Minz Madhulika Pradhan Nitin Deshmukh |
| author_sort | Mohini Patidar |
| collection | DOAJ |
| description | Background: Diabetes mellitus is a long-standing and debilitating metabolic condition that imposes a substantial global health burden, leading to severe and widespread complications. Objectives: This study aims to predict physicochemical properties of 1,3,4-oxadiazole derivatives using in-silico methods and molecular docking simulations to explore their potential as α-glucosidase inhibitors for diabetes management. Furthermore, this study aims to experimentally synthesize and characterize these derivatives to validate their inhibitory activity. Methods: In silico drug-likeness, pharmacokinetic, and toxicity profiling of substituted oxadiazole derivatives were performed using the Molinspiration and PreADMET web tools. Molecular docking simulations were conducted with the target protein alpha-glucosidase (PDB ID: 3WY1) to assess its anti-diabetic potential. This study suggests that oxadiazole has the potential to be a novel anti-diabetic agent. Results: Compound 3a1 formed 5 significant hydrogen bonds with Gly228, Thr226, Leu227, Tyr235, Glu271 with docking scores of -156.118 and re-rank scores of -91.600 comparable to the standard drug Miglitol, which formed 6 hydrogen bonds Val380, Asp401, Lys398, Gly399, Glu377, Asp379 but had lower docking and re-rank scores (-69.4415 and -95.887). Based on docking results, five oxadiazole derivatives were synthesized via Mannich base cyclization, yielding 62.2 – 79.9%. They showed moderate to excellent anti-diabetic activity, with compounds 3a1 and 3a3 demonstrating no toxicity or mortality at 40 mg/kg oral dose. Conclusion: Our study highlights that the oxadiazole pharmacophore is a key structural motif for the development of potential anti-diabetic compounds |
| format | Article |
| id | doaj-art-45a76526665f43209535ced574ccaa23 |
| institution | DOAJ |
| issn | 2348-0335 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Creative Pharma Assent |
| record_format | Article |
| series | Journal of Applied Pharmaceutical Research |
| spelling | doaj-art-45a76526665f43209535ced574ccaa232025-08-20T03:10:10ZengCreative Pharma AssentJournal of Applied Pharmaceutical Research2348-03352025-04-0113219420310.69857/joapr.v13i2.10311032A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agentsMohini Patidar0Raghvendra Dubey1Sunita Minz2Madhulika Pradhan3Nitin Deshmukh4Department of Pharmaceutical Chemistry, Sage University: Institute of Pharmaceutical Sciences, Indore, 452016, IndiaDepartment of Pharmaceutical Chemistry, Sage University: Institute of Pharmaceutical Sciences, Indore, 452016, India Department of Pharmaceutics, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, IndiaGracious College of Pharmacy, Abhanpur, Chhattisgarh, India 493661Department of Pharmaceutical Chemistry, Mangaldeep Institute of Pharmacy, Aurangabad, Maharashtra 431001Background: Diabetes mellitus is a long-standing and debilitating metabolic condition that imposes a substantial global health burden, leading to severe and widespread complications. Objectives: This study aims to predict physicochemical properties of 1,3,4-oxadiazole derivatives using in-silico methods and molecular docking simulations to explore their potential as α-glucosidase inhibitors for diabetes management. Furthermore, this study aims to experimentally synthesize and characterize these derivatives to validate their inhibitory activity. Methods: In silico drug-likeness, pharmacokinetic, and toxicity profiling of substituted oxadiazole derivatives were performed using the Molinspiration and PreADMET web tools. Molecular docking simulations were conducted with the target protein alpha-glucosidase (PDB ID: 3WY1) to assess its anti-diabetic potential. This study suggests that oxadiazole has the potential to be a novel anti-diabetic agent. Results: Compound 3a1 formed 5 significant hydrogen bonds with Gly228, Thr226, Leu227, Tyr235, Glu271 with docking scores of -156.118 and re-rank scores of -91.600 comparable to the standard drug Miglitol, which formed 6 hydrogen bonds Val380, Asp401, Lys398, Gly399, Glu377, Asp379 but had lower docking and re-rank scores (-69.4415 and -95.887). Based on docking results, five oxadiazole derivatives were synthesized via Mannich base cyclization, yielding 62.2 – 79.9%. They showed moderate to excellent anti-diabetic activity, with compounds 3a1 and 3a3 demonstrating no toxicity or mortality at 40 mg/kg oral dose. Conclusion: Our study highlights that the oxadiazole pharmacophore is a key structural motif for the development of potential anti-diabetic compoundshttps://japtronline.com/index.php/joapr/article/view/1031mannich bases reactionanti-diabetic effects1,3,4-oxadiazole derivatives |
| spellingShingle | Mohini Patidar Raghvendra Dubey Sunita Minz Madhulika Pradhan Nitin Deshmukh A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents Journal of Applied Pharmaceutical Research mannich bases reaction anti-diabetic effects 1,3,4-oxadiazole derivatives |
| title | A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents |
| title_full | A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents |
| title_fullStr | A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents |
| title_full_unstemmed | A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents |
| title_short | A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents |
| title_sort | mechanism driven strategy for in silico prediction molecular docking synthesis and biological assessment of substituted 1 3 4 oxadiazole derivatives as novel antidiabetic agents |
| topic | mannich bases reaction anti-diabetic effects 1,3,4-oxadiazole derivatives |
| url | https://japtronline.com/index.php/joapr/article/view/1031 |
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