Comprehending the inhibition mechanism of indole-based bis-acylhydrazone compounds on α-glucosidase: Spectral and theoretical approaches.

Autor: Jiang SL; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: shljiang@zjut.edu.cn., Hu ZY; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China., Sui HY; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China., Huang T; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China., Han L; College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, China., Hu CM; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China., Xu XT; School of Pharmacy and Food Engineering, Wuyi University, Jiangmen 529020, China. Electronic address: wyuchemxxt@126.com., Shi JH; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China., Chu C; College of Pharmaceutic Science, Zhejiang University of Technology, Hangzhou 310032, China.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Sep; Vol. 276 (Pt 1), pp. 133489. Date of Electronic Publication: 2024 Jul 02.
DOI: 10.1016/j.ijbiomac.2024.133489
Abstrakt: Indole-based bis-acylhydrazone compounds can inhibit the activity of α-glucosidase and control the concentration of blood glucose. In this paper, the characteristics of three indole-based bis-acylhydrazone compounds with different inhibitory activities of α-glucosidase as well as the interaction with α-glucosidase were studied by experiments and computational simulation techniques. Enzyme kinetic and spectral experiments showed that the indole-based bis-acylhydrazone compounds were able to inhibit enzyme activity through mixed inhibition dominated by competitive inhibition, and during the binding reaction, indole-based bis-acylhydrazone compounds can quench the intrinsic fluorescence of α-glucosidase through static quenching and an aggregation of the indole-based bis-acylhydrazone with α-glucosidase produces a stable complex with a molar ratio of 1:1, and the combination of indole-based bis-acylhydrazone compounds could lead to slight change in the conformation of α-glucosidase. The theoretical simulation demonstrated that the stability of the complex systems was positively correlated with the inhibitory activity of indole-based bis-acylhydrazone compounds, and the indole-based bis-acylhydrazone compounds occupied the active site in the multi-ligand system, resulting in a significant decrease in the binding ability of starch to active amino acids. These results suggested that indole-based bis-acylhydrazone compound was expected to be a new type of α-glucosidase inhibitor.
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.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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