Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment
Abstract The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking iden...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11214-4 |
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| author | Mohammed A. Marzouk Elsayed M. Mahmoud Wesam S. Shehab Sherif M. Fawzy Samar M. Mohammed Mahmoud Ashraf Abdel-Razek Ghada E. Khedr Doaa A. Elsayed |
| author_facet | Mohammed A. Marzouk Elsayed M. Mahmoud Wesam S. Shehab Sherif M. Fawzy Samar M. Mohammed Mahmoud Ashraf Abdel-Razek Ghada E. Khedr Doaa A. Elsayed |
| author_sort | Mohammed A. Marzouk |
| collection | DOAJ |
| description | Abstract The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking identified six promising candidates, with compounds 4 and 10 showing the highest potency. Both compounds exhibited strong α-glucosidase inhibition (IC50 = 0.27 ± 0.01 µg/mL and 0.31 ± 0.01 μg/mL, respectively), surpassing acarbose, and also demonstrated potent α-amylase inhibition (IC50 = 0.19 ± 0.01 μg/mL and 0.26 ± 0.01 μg/mL, respectively). Structure–activity relationship analysis highlighted the crucial role of acetyl and bromo substituents in enhancing enzyme inhibition. These findings position triazole-based scaffolds as promising candidates for the development of next-generation antidiabetic therapies. |
| format | Article |
| id | doaj-art-0a693ffe31b7429ca3c215bab68bf596 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0a693ffe31b7429ca3c215bab68bf5962025-08-20T04:02:46ZengNature PortfolioScientific Reports2045-23222025-07-0115112010.1038/s41598-025-11214-4Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatmentMohammed A. Marzouk0Elsayed M. Mahmoud1Wesam S. Shehab2Sherif M. Fawzy3Samar M. Mohammed4Mahmoud Ashraf Abdel-Razek5Ghada E. Khedr6Doaa A. Elsayed7Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig UniversityDepartment of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig UniversityDepartment of Chemistry, Faculty of Science, Zagazig UniversityDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai UniversityDepartment of Chemistry, Faculty of Science, Zagazig UniversityMicrobiology and Immunology Department, Faculty of Pharmacy, Zagazig UniversityDepartment of Analysis and Evaluation, Egyptian Petroleum Research InstituteDepartment of Chemistry, Faculty of Science, Zagazig UniversityAbstract The development of effective antidiabetic agents remains a critical challenge in diabetes management. In this study, we introduce novel 1,2,4-triazole-based derivatives designed as dual inhibitors of α-amylase and α-glucosidase, key enzymes in carbohydrate metabolism. Molecular docking identified six promising candidates, with compounds 4 and 10 showing the highest potency. Both compounds exhibited strong α-glucosidase inhibition (IC50 = 0.27 ± 0.01 µg/mL and 0.31 ± 0.01 μg/mL, respectively), surpassing acarbose, and also demonstrated potent α-amylase inhibition (IC50 = 0.19 ± 0.01 μg/mL and 0.26 ± 0.01 μg/mL, respectively). Structure–activity relationship analysis highlighted the crucial role of acetyl and bromo substituents in enhancing enzyme inhibition. These findings position triazole-based scaffolds as promising candidates for the development of next-generation antidiabetic therapies.https://doi.org/10.1038/s41598-025-11214-41,2,4-Triazole derivativesAnti-diabetic activityα-Amylase inhibitorsα-Glucosidase inhibitorsMolecular docking analysisIn vitro enzyme inhibition |
| spellingShingle | Mohammed A. Marzouk Elsayed M. Mahmoud Wesam S. Shehab Sherif M. Fawzy Samar M. Mohammed Mahmoud Ashraf Abdel-Razek Ghada E. Khedr Doaa A. Elsayed Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment Scientific Reports 1,2,4-Triazole derivatives Anti-diabetic activity α-Amylase inhibitors α-Glucosidase inhibitors Molecular docking analysis In vitro enzyme inhibition |
| title | Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment |
| title_full | Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment |
| title_fullStr | Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment |
| title_full_unstemmed | Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment |
| title_short | Dual α-amylase and α-glucosidase inhibition by 1,2,4-triazole derivatives for diabetes treatment |
| title_sort | dual α amylase and α glucosidase inhibition by 1 2 4 triazole derivatives for diabetes treatment |
| topic | 1,2,4-Triazole derivatives Anti-diabetic activity α-Amylase inhibitors α-Glucosidase inhibitors Molecular docking analysis In vitro enzyme inhibition |
| url | https://doi.org/10.1038/s41598-025-11214-4 |
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