Novel carbazole-oxadiazole derivatives as anti-α-glucosidase and anti-α-amylase agents: Design, synthesis, molecular docking, and biological evaluation.

Autor: Luo S; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; School of Pharmacy, Guizhou Medical University, Guiyang, China., Zhao L; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; School of Pharmacy, Guizhou Medical University, Guiyang, China., Peng H; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China; School of Pharmacy, Guizhou Medical University, Guiyang, China., Peng Z; Clinical Trails Center, The Affiliated Hospital of Guizhou Medical University, Guiyang, China. Electronic address: pengzhiyun1986@163.com., Wang G; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China. Electronic address: wanggch123@163.com.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2024 Sep 05; Vol. 275, pp. 116600. Date of Electronic Publication: 2024 Jun 14.
DOI: 10.1016/j.ejmech.2024.116600
Abstrakt: To find novel inhibitors of α-glucosidase and α-amylase, a series of new carbazole-oxadiazole derivatives (6a-6n) were prepared, and screened for their anti-α-glucosidase and anti-α-amylase effects. Most of the tested derivatives showed different degrees of α-glucosidase and α-amylase inhibitory activity (IC 50 : 21.39 ± 0.69-92.05 ± 1.54 μM, 45.53 ± 1.50-126.14 ± 6.33 μM, respectively) compared to the standard acarbose (IC 50 : 427.00 ± 9.56 μM, 24.68 ± 1.10 μM, respectively). Thereinto, 6c (IC 50  = 21.39 ± 0.69 μM) displayed the most effective anti-α-glucosidase activity and 6e presented the best anti-α-amylase activity with an IC 50 value of 45.53 ± 1.50 μM. Lineweaver-Burk plot analysis suggested that 6c and 6e behaved as mixed α-glucosidase inhibitor and mixed α-amylase inhibitor, respectively. The results of circular dichroism, atomic force microscope, and molecular docking simulation exposed interaction mechanisms between two preferred compounds (6c and 6e) and their corresponding enzymes. Combined with the possible properties of reducing the elevation in postprandial blood glucose, oral activity, positive bioavailability, and low cytotoxicity of 6c and 6e, it could be concluded that the target derivatives may be able to act as lead molecules for the development of new hypoglycemic agents.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Databáze: MEDLINE
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