Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents
Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeu...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | European Journal of Medicinal Chemistry Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772417424000797 |
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| author | Mehdi Valipour Zahra Zakeri Khatir Kaveh Kiadaliry Somayeh Mojtabavi Mohammad Ali Faramarzi Mohammad Shokati Sayyad Mohammad Seyedabadi Majid Ghasemian Seyedeh Mahdieh Hashemi Hamid Irannejad |
| author_facet | Mehdi Valipour Zahra Zakeri Khatir Kaveh Kiadaliry Somayeh Mojtabavi Mohammad Ali Faramarzi Mohammad Shokati Sayyad Mohammad Seyedabadi Majid Ghasemian Seyedeh Mahdieh Hashemi Hamid Irannejad |
| author_sort | Mehdi Valipour |
| collection | DOAJ |
| description | Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC50 = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC50 values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus. |
| format | Article |
| id | doaj-art-3a15142535f74b009bfc0fa2c9c502f6 |
| institution | Kabale University |
| issn | 2772-4174 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | European Journal of Medicinal Chemistry Reports |
| spelling | doaj-art-3a15142535f74b009bfc0fa2c9c502f62024-12-05T05:21:54ZengElsevierEuropean Journal of Medicinal Chemistry Reports2772-41742024-12-0112100207Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agentsMehdi Valipour0Zahra Zakeri Khatir1Kaveh Kiadaliry2Somayeh Mojtabavi3Mohammad Ali Faramarzi4Mohammad Shokati Sayyad5Mohammad Seyedabadi6Majid Ghasemian7Seyedeh Mahdieh Hashemi8Hamid Irannejad9Razi Drug Research Center, Iran University of Medical Sciences, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, IranDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmaceutical Biotechnology, Faculty of Pharmacy and Biotechnology Research Center, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, IranDepartment of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, IranDepartment of Clinical Biochemistry, Faculty of Medicine, Jundishapur University of Medical Sciences, Ahvaz, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran; Corresponding author.Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC50 = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC50 values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.http://www.sciencedirect.com/science/article/pii/S2772417424000797Diabetes mellitus1,2,4-TriazineSynthesisα-glucosidaseHyperglycemia |
| spellingShingle | Mehdi Valipour Zahra Zakeri Khatir Kaveh Kiadaliry Somayeh Mojtabavi Mohammad Ali Faramarzi Mohammad Shokati Sayyad Mohammad Seyedabadi Majid Ghasemian Seyedeh Mahdieh Hashemi Hamid Irannejad Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents European Journal of Medicinal Chemistry Reports Diabetes mellitus 1,2,4-Triazine Synthesis α-glucosidase Hyperglycemia |
| title | Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents |
| title_full | Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents |
| title_fullStr | Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents |
| title_full_unstemmed | Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents |
| title_short | Design, synthesis, α-glucosidase inhibition and hypoglycemic activity of 3-aceto(benzo)hydrazide-1,2,4-triazines as potential anti-diabetic agents |
| title_sort | design synthesis α glucosidase inhibition and hypoglycemic activity of 3 aceto benzo hydrazide 1 2 4 triazines as potential anti diabetic agents |
| topic | Diabetes mellitus 1,2,4-Triazine Synthesis α-glucosidase Hyperglycemia |
| url | http://www.sciencedirect.com/science/article/pii/S2772417424000797 |
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