Inhibition Mechanism of 3-Hydroxyflavones Against α-Glucosidase: Published online: 26/03/2026

Journal of Technical Education Science - Trang - 2026
Lieu Quang Le1, Luc Tien Nguyen2, Tan Thanh Mai3, Suc Van Nguyen2, Phuong Ho2, Hao Minh Hoang2
1College of Fisheries and Food Technology, Vietnam
2Ho Chi Minh City University of Technology and Education, Vietnam
3School of Pharmacy, University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam

Tóm tắt

3-Hydroxyflavones belong to a subgroup of flavonoids that exhibit a broad range of bioactivities. In this respect, diverse 3-hydroxyflavones have been isolated from natural sources and synthesized in laboratories through different chemical routes to search for analogs with promising bioactivities. As part of our ongoing research into the α-glucosidase inhibition of synthesized 3-hydroxyflavones, we herein screened for the α-glucosidase inhibitory activity of 3-hydroxyflavones. Among the tested compounds (1-5), for the first time, two fluorinated derivatives (compounds 4 and 5), bearing fluoro substituents at the 4′- and 3′,4′-positions of the B ring were active, presenting IC50 values of 326.47±0.79 µM and 373.74±1.83 µM, respectively. The intrinsic fluorescence spectra of α-glucosidase were quenched gradually with increasing amounts of inhibitors 4 and 5, indicating both inhibitors were bound to α-glucosidase. Furthermore, when 8-anilino-1-naphthalenesulfonic acid (ANS), an extrinsic fluorescence probe was added to the enzyme solution, the fluorescence intensity of [α-glucosidase-ANS] complex was reduced, suggesting that 3-hydroxyflavone 4 and 5 interacted with the enzyme via hydrophobic domain. Finally, inhibitory kinetic analysis using Lineweaver-Burk plots was also applied for both selected inhibitors. It was found that compounds 4 and 5 acted as competitive inhibitors of α-glucosidase.

Từ khóa

#3-Hydroxyflavones #α-Glucosidase #Fluorescence quenching #Lineweaver-Burk plots #Competitive inhibition

Tài liệu tham khảo

A. Salsali and M. Nathan, “A review of types 1 and 2 diabetes mellitus and their treatment with insulin,” Am. J. Ther., vol. 13, no. 4, pp. 349–361, Jul. 2006, doi: 10.1097/00045391-200607000-00012.

A. B. Olokoba, O. A. Obateru, and L. B. Olokoba, “Type 2 diabetes mellitus: a review of current trends,” Oman Med. J., vol. 27, no. 4, pp. 269–273, Jul. 2012, doi: 10.5001/omj.2012.68.

S. R. Joshi, E. Standl, N. Tong, P. Shah, S. Kalra, and R. Rathod, “Therapeutic potential of α-glucosidase inhibitors in type 2 diabetes mellitus: an evidence-based review,” Expert Opin. Pharmacother., vol. 16, no. 13, pp. 1959–1981, Sep. 2015, doi: 10.1517/14656566.2015.1070827.

R. Sudhir and V. Mohan, “Postprandial hyperglycemia in patients with type 2 diabetes mellitus,” Treat. Endocrinol., vol. 1, no. 2, pp. 105–116, 2002, doi: 10.2165/00024677-200201020-00004.

I. Erlund, “Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology,” Nutr. Res., vol. 24, no. 10, pp. 851–874, Oct. 2004, doi: 10.1016/j.nutres.2004.07.005.

C. Proença et al., “α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study,” J. Enzyme Inhib. Med. Chem., vol. 32, no. 1, pp. 1216–1228, Jan. 2017, doi: 10.1080/14756366.2017.1368503.

C. He, X. Liu, Z. Jiang, S. Geng, H. Ma, and B. Liu, “Interaction mechanism of flavonoids and α-glucosidase: experimental and molecular modelling studies,” Foods, vol. 8, no. 9, p. 355, Aug. 2019, doi: 10.3390/foods8090355.

W. Kho et al., “Strain-specific anti-biofilm and antibiotic-potentiating activity of 3′,4′-difluoroquercetin,” Sci. Rep., vol. 10, no. 1, p. 14162, Aug. 2020, doi: 10.1038/s41598-020-71025-7.

C. Conti, P. Mastromarino, P. Goldoni, G. Portalone, and N. Desideri, “Synthesis and anti-rhinovirus properties of fluoro-substituted flavonoids,” Antivir. Chem. Chemother., vol. 16, no. 4, pp. 267–276, Aug. 2005, doi: 10.1177/095632020501600406.

H. T. Le et al., “Synthesis of novel fluorinated flavonols via Algar–Flynn–Oyamada reaction,” unpublished.

V. T. Nga and H. M. Hao, “Inhibition kinetics and mechanism of genistein against α‐glucosidase,” Vietnam J. Chem., vol. 62, no. 4, pp. 493–499, Aug. 2024, doi: 10.1002/vjch.202200173.

P. Ho, D. P. Nguyen, K. D. Dang, and H. M. Hoang, “Comparison of quenching kinetics and mechanism of tryptophan by acrylamide and genistein studied by fluorescence spectroscopy,” J. Tech. Educ. Sci., vol. 20, no. 02, pp. 20–25, May 2025, doi: 10.54644/jte.2025.1568.

J. R. Lakowicz, Principles of fluorescence spectroscopy, 3rd ed. New York: Springer, 2006.

B. E. Smart, “Fluorine substituent effects (on bioactivity),” J. Fluor. Chem., vol. 109, no. 1, pp. 3–11, Jun. 2001, doi: 10.1016/S0022-1139(01)00375-X.

L. Jiang, Z. Wang, X. Wang, S. Wang, J. Cao, and Y. Liu, “Exploring the inhibitory mechanism of piceatannol on α-glucosidase relevant to diabetes mellitus,” RSC Adv., vol. 10, no. 8, pp. 4529–4537, 2020, doi: 10.1039/C9RA09028B.

X. Zhang et al., “Screening of α‐glucosidase inhibitors from houttuynia cordata and evaluation of the binding mechanisms,” ChemistrySelect, vol. 5, no. 28, pp. 8440–8446, Jul. 2020, doi: 10.1002/slct.202001657.

A. Hawe, M. Sutter, and W. Jiskoot, “Extrinsic fluorescent dyes as tools for protein characterization,” Pharm. Res., vol. 25, no. 7, pp. 1487–1499, Jul. 2008, doi: 10.1007/s11095-007-9516-9.

M. Deshpande and S. K. Sathe, “Interactions with 8‐anilinonaphthalene‐1‐sulfonic Acid (ANS) and surface hydrophobicity of black Gram ( Vigna mungo ) Phaseolin,” J. Food Sci., vol. 83, no. 7, pp. 1847–1855, Jul. 2018, doi: 10.1111/1750-3841.14204.

O. K. Gasymov and B. J. Glasgow, “ANS fluorescence: Potential to augment the identification of the external binding sites of proteins,” Biochim. Biophys. Acta BBA - Proteins Proteomics, vol. 1774, no. 3, pp. 403–411, Mar. 2007, doi: 10.1016/j.bbapap.2007.01.002.

A. Rogers and Y. Gibon, “Enzyme Kinetics: Theory and practice,” in Plant Metabolic Networks, J. Schwender, Ed., New York, NY: Springer New York, 2009, pp. 71–103. doi: 10.1007/978-0-387-78745-9_4.

H. Lineweaver and D. Burk, “the determination of enzyme dissociation constants,” J. Am. Chem. Soc., vol. 56, no. 3, pp. 658–666, Mar. 1934, doi: 10.1021/ja01318a036.

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