Synthesis and biological evaluation of novel chromonyl enaminones as α-glucosidase inhibitors

Mendieta‐Moctezuma, Aarón; Rugerio-Escalona, Catalina; Villa‐Ruano, Nemesio; Gutiérrez, Rsuini U.; Jiménez-Montejo, Fabiola E.; Fragoso-Vázquez, Manuel Jonathan; Correa‐Basurto, José; Cruz-López, María C.; Delgado, Francisco; Tamariz, Joaquı́n

doi:10.1007/s00044-019-02320-w

Cited by 11 publications

(3 citation statements)

References 49 publications

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“…Irradiation of the signal assigned to the methyl protons of the dimethylamine group produced the enhancement of the signal corresponding to the aryloxy ring of the xanthone scaffold. This stereoselectivity has been observed in similar systems, probably because of the greater stability of the planar π-conjugated acrylate system when the bulky dimethylamine group is located at the opposite side of the double bond [ 46 ].…”

Section: Resultsmentioning

confidence: 66%

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors

Aguila-Muñoz,

Vázquez-Lira,

Sarmiento-Tlale

et al. 2023

Molecules

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Current antidiabetic drugs have severe side effects, which may be minimized by new selective molecules that strongly inhibit α-glucosidase and weakly inhibit α-amylase. We have synthesized novel alkoxy-substituted xanthones and imidazole-substituted xanthones and have evaluated them for their in silico and in vitro α-glucosidase and α-amylase inhibition activity. Compounds 6c, 6e, and 9b promoted higher α-glucosidase inhibition (IC50 = 16.0, 12.8, and 4.0 µM, respectively) and lower α-amylase inhibition (IC50 = 76.7, 68.1, and >200 µM, respectively) compared to acarbose (IC50 = 306.7 µM for α-glucosidase and 20.0 µM for α-amylase). Contrarily, derivatives 10c and 10f showed higher α-amylase inhibition (IC50 = 5.4 and 8.7 µM, respectively) and lower α-glucosidase inhibition (IC50 = 232.7 and 145.2 µM, respectively). According to the structure–activity relationship, attaching 4-bromobutoxy or 4′-chlorophenylacetophenone moieties to the 2-hydroxy group of xanthone provides higher α-glucosidase inhibition and lower α-amylase inhibition. In silico studies suggest that these scaffolds are key in the activity and interaction of xanthone derivatives. Enzymatic kinetics studies showed that 6c, 9b, and10c are mainly mixed inhibitors on α-glucosidase and α-amylase. In addition, drug prediction and ADMET studies support that compounds 6c, 9b, and 10c are candidates with antidiabetic potential.

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Section: Resultsmentioning

confidence: 66%

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors

Aguila-Muñoz,

Vázquez-Lira,

Sarmiento-Tlale

et al. 2023

Molecules

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“…The synthesis of 3-nitro-4H-chromen-4-one was achieved in 82% yield from the reaction of 2 0 -hydroxy-2-nitroacetophenone with triethyl orthoformate and concentrated sulfuric acid in refluxing conditions for 6 h. 331 The reaction of 2-alkyl-1-(2-hydroxyaryl)ethan-1-ones with DMF-DMA at reflux at 120 °C for 48 h led to formation of some 3-alkyl-4H-chromen-4-ones, in moderate to excellent yields. 332…”

Section: Scheme 44mentioning

confidence: 99%

Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

Santos

Silva

2022

Advances in Heterocyclic Chemistry

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“…α-Glucosidase is an indispensable enzyme in the sugar metabolism pathway of organisms, and its main function is to hydrolyze glycosidic bonds into glucose ( Chaudhry et al, 2019 ; Dan et al, 2019 ; Gollapalli et al, 2019 ; Krishna et al, 2019 ; Mendieta-Moctezuma et al, 2019 ; Spasov et al, 2019 ; Ye et al, 2019 ). Thus inhibiting the α-glucosidase would obviously control the postprandial hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors

Lin

Liang

et al. 2022

Front. Chem.

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α-Glucosidase inhibitors are known to prevent the digestion of carbohydrates and reduce the impact of carbohydrates on blood glucose. To develop novel α-glucosidase inhibitors, a series of 5-fluoro-2-oxindole derivatives (3a ∼ 3v) were synthesized, and their α-glucosidase inhibitory activities were investigated. Biological assessment results showed that most synthesized compounds presented potential inhibition on α-glucosidase. Among them, compounds 3d, 3f, and 3i exhibited much better inhibitory activity with IC50 values of 49.89 ± 1.16 μM, 35.83 ± 0.98 μM, and 56.87 ± 0.42 μM, respectively, which were about 10 ∼ 15 folds higher than acarbose (IC50 = 569.43 ± 43.72 μM). A kinetic mechanism study revealed that compounds 3d, 3f, and 3i inhibited the α-glucosidase in a reversible and mixed manner. Molecular docking was carried out to simulate the affinity between the compound and α-glucosidase.

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Synthesis and biological evaluation of novel chromonyl enaminones as α-glucosidase inhibitors

Cited by 11 publications

References 49 publications

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors

Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

Synthesis and Biological Evaluation of 5-Fluoro-2-Oxindole Derivatives as Potential α-Glucosidase Inhibitors

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