2. Academic Validation
  3. Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2- a]pyridine Derivatives

Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2- a]pyridine Derivatives

  • ACS Omega. 2024 Oct 11;9(42):42905-42914. doi: 10.1021/acsomega.4c05619.
Betül Kaya 1,  Ulviye Acar Çevik 2,  Bilge Çiftçi 3,  Hatice Esra Duran 4,  Cüneyt Türkeş 5,  Mesut Işık 6,  Hayrani Eren Bostancı 7,  Zafer Asım Kaplancıklı 2,  Şükrü Beydemir 8
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bulent Ecevit University, 67600 Zonguldak, Turkey.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 3 Vocational School of Health Services, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
  • 4 Department of Medical Biochemistry, Faculty of Medicine, Kafkas University, 36100 Kars, Turkey.
  • 5 Department of Biochemistry, Faculty of Pharmacy, Erzincan Binali Yıldırım University, 24002 Erzincan, Turkey.
  • 6 Department of Bioengineering, Faculty of Engineering, Bilecik Şeyh Edebali University, 11230 Bilecik, Turkey.
  • 7 Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkey.
  • 8 Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
PMID: 39464438 DOI: 10.1021/acsomega.4c05619
Abstract

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).

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