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

• Published in: International journal of biological macromolecules 2024-09, Vol.276 (Pt 1), p.133489, Article 133489
• Main Authors: Jiang, Shao-Liang, Hu, Zhe-Ying, Sui, Huan-Yu, Huang, Teng, Han, Liang, Hu, Chun-Mei, Xu, Xue-Tao, Shi, Jie-Hua, Chu, Chu
• Format: Article
• Language: English
• Subjects: Computational simulation; Indole-based bis-acylhydrazone; Spectroscopy; α-Glucosidase
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.133489

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. •Three indole-based bis-acylhydrazone compounds (A, B and C) inhibit α-glucosidase in the mixed inhibition mode.•The binding mechanism of compounds were analyzed by experiments and simulation.•Relationship between inhibitory activity and binding characteristics of compounds A, B and C•Compounds A, B and C occupied the active site of α-glucosidase.