Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies
Yıl: 2023 Cilt: 16 Sayı: 2 Sayfa Aralığı: 345 - 356 Metin Dili: İngilizce DOI: 10.18185/erzifbed.1216717 İndeks Tarihi: 11-09-2023
Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies
Öz: Diabetes mellitus (DM) is a metabolic disease that causes an increase in blood glucose levels, leading to postprandial hyperglycemia and numerous secondary problems, such as kidney failure, blindness, cardiovascular diseases, and nerve damage. Inhibitors of α amylase and α glucosidase are widely used in the treatment of type-II DM because they can inhibit the digestion of starch. In this study, the inhibition potentials of previously synthesized fluorine-containing 1,2,4-triazole-5-one derivatives (4a-d, 6a-b, 7a-b, 8a-b) were screened against α-amylase and α-glucosidase activities. All the compounds exhibited varying degrees of α- amylase inhibitory potential, ranging from 185.2 ± 3.4 to 535.6 ± 5.5 μM. For α-glucosidase, the IC50 values ranged from 202.1 ± 3.8 to 803.2 ± 10.3 μM, compared to the positive control acarbose (IC50 = 411.3 ± 6.4 μM for α-amylase and IC50 = 252.0 ± 4.8 μM for α-glucosidase). 4c exhibited excellent inhibitory potential in both cases, and we evaluated the mode of inhibition of α-amylase and α-glucosidase through kinetic studies. Furthermore, we calculated the physicochemical and pharmacokinetic properties of molecule 4c using SwissADME software. The results of our research suggest that compound 4c may be a promising candidate for the treatment of type-II DM.
Anahtar Kelime: 1,2,4-Triazol Türevlerinin Potansiyel Anti-Diyabetik Ajanlar Olarak Araştırılması: In vitro Enzim İnhibisyonu ve In Silico Farmakokinetik Çalışmaları
Öz: Diabetes Mellitus (DM), kan glukoz seviyesinin yükseldiği, postprandiyal hiperglisemiye neden olan, böbrek yetmezliği, körlük, kardiyovasküler hastalıklar ve sinir hasarı gibi pek çok sekonder probleme neden olan metabolik bir hastalıktır. α-Amilaz ve α-glukozidaz doğrudan tip II DM ile ilgilidir ve bu enzimlerin inhibitörleri nişasta sindirimini inhibe edebildiğinden DM tedavisinde yaygın olarak kullanılmaktadır. Bu çalışmada daha önce sentezlenen flor içeren 1,2,4-triazol-5-on türevlerinin (4a-d, 6a-b, 7a-b, 8a-b) α-amilaz ve α-glukozidaza karşı inhibisyon potansiyelleri araştırıldı. Tüm moleküller, pozitif kontrol akarboza kıyasla (α-amilaz için IC50 = 411,3 ± 6,4 uM, α-glukozidaz için IC50 = 252,0 ± 4,8 μM), 185,2 ± 3,4 ila 535,6 ± 5,5 μM arasında değişen farklı oranlarda α-amilaz inhibisyonu sergiledi; α-glukozidaz varlığında ise, IC50 değerleri 205,0 ± 3,8 ila 803,2 ± 10,3 μM arasında değişim gösterdi. 10 farklı inhibitör molekülü arasında 4c'nin her iki durumda da mükemmel inhibe edici potansiyele sahip olduğu tespit edildi ve α-amilaz ve α-glukozidazın inhibisyon türü kinetik çalışmalarla değerlendirildi. Ayrıca SwissADME yazılımı kullanılarak 4c molekülünün fizikokimyasal ve farmakokinetik özellikleri hesaplandı. Mevcut araştırmanın sonuçları, tip II DM'nin tedavisi için umut vaat eden bir aday olarak 4c molekülünün potansiyelini desteklemektedir.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | Öz Tuncay F, cakmak u (2023). Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. , 345 - 356. 10.18185/erzifbed.1216717 |
| Chicago | Öz Tuncay Fulya,cakmak ummuhan Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. (2023): 345 - 356. 10.18185/erzifbed.1216717 |
| MLA | Öz Tuncay Fulya,cakmak ummuhan Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. , 2023, ss.345 - 356. 10.18185/erzifbed.1216717 |
| AMA | Öz Tuncay F,cakmak u Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. . 2023; 345 - 356. 10.18185/erzifbed.1216717 |
| Vancouver | Öz Tuncay F,cakmak u Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. . 2023; 345 - 356. 10.18185/erzifbed.1216717 |
| IEEE | Öz Tuncay F,cakmak u "Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies." , ss.345 - 356, 2023. 10.18185/erzifbed.1216717 |
| ISNAD | Öz Tuncay, Fulya - cakmak, ummuhan. "Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies". (2023), 345-356. https://doi.org/10.18185/erzifbed.1216717 |
| APA | Öz Tuncay F, cakmak u (2023). Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 16(2), 345 - 356. 10.18185/erzifbed.1216717 |
| Chicago | Öz Tuncay Fulya,cakmak ummuhan Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi 16, no.2 (2023): 345 - 356. 10.18185/erzifbed.1216717 |
| MLA | Öz Tuncay Fulya,cakmak ummuhan Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi, vol.16, no.2, 2023, ss.345 - 356. 10.18185/erzifbed.1216717 |
| AMA | Öz Tuncay F,cakmak u Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2023; 16(2): 345 - 356. 10.18185/erzifbed.1216717 |
| Vancouver | Öz Tuncay F,cakmak u Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies. Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2023; 16(2): 345 - 356. 10.18185/erzifbed.1216717 |
| IEEE | Öz Tuncay F,cakmak u "Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies." Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 16, ss.345 - 356, 2023. 10.18185/erzifbed.1216717 |
| ISNAD | Öz Tuncay, Fulya - cakmak, ummuhan. "Investigation of 1,2,4-Triazole Derivatives as Potantial Anti-Diabetic Agents: In vitro Enzyme Inhibition and In silico Pharmacokinetic Studies". Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi 16/2 (2023), 345-356. https://doi.org/10.18185/erzifbed.1216717 |
