A review on synthesis, mechanism of action, and structure-activity relationships of 1,2,3-triazole-based α-glucosidase inhibitors as promising anti-diabetic agents

Fallah, Zari; Tajbakhsh, Mahmood; Ali, Majid; Larijani, Bagher; Faramarzi, Mohammad Ali; Hamedifar, Haleh; Mohammadi‐Khanaposhtani, Maryam; Mahdavi, Mohammad

doi:10.1016/j.molstruc.2022.132469

Cited by 62 publications

(30 citation statements)

References 81 publications

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“…Among many click reactions described to date, copper (I)-catalyzed alkyne-azide cycloaddition introduced by Sharpless et al 26 has attracted much attention due to the potency of production of a library of bioactive 1,2,3-triazole derivatives through heteroatom links 27 – 32 . The α-glucosidase inhibitory activity of 1,2,3-triazoles have also been fully investigated in the literature 33 as a prime choice for medicinal researchers to develop new anti-DM molecules.…”

Section: Introductionmentioning

confidence: 99%

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Iraji

Shareghi-Brojeni

Mojtabavi

et al. 2022

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In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

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Section: Introductionmentioning

confidence: 99%

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Iraji

Shareghi-Brojeni

Mojtabavi

et al. 2022

Sci Rep

Self Cite

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“…Triazole is an important nitrogen heterocyclic compound, containing three nitrogen atoms and two carbon atoms. It had reported that compounds containing triazole have an important application value in various fields, such as ( Brüggemann et al, 2022 ; Fallah et al, 2022 ; Sharma et al, 2022 ) agrochemistry ( Georgiadis et al, 2018 ; Musarurwa and Tavengwa, 2021 ; Valencia-Quintana et al, 2022 ) and material chemistry ( Scattergood et al, 2017 ; Rodrigues et al, 2020 ; Ahmed and Xiong, 2021 ). Its unique structure facilitates the formation of a variety of non-covalent bonds with enzymes and receptors inducing broad-spectrum biological activities, such as anticancer ( Sharma et al, 2022 ), antituberculosis ( Keri et al, 2015 ; Zhang et al, 2017 ), antibacterial ( Gao et al, 2019 ; Zhang, 2019 ; Strzelecka and Swiatek, 2021 ), and anti-HIV ( Patel et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis methods of 1,2,3-/1,2,4-triazoles: A review

et al. 2022

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Triazole, comprising three nitrogen atoms and two carbon atoms, is divided into two isomers 1,2,3-triazole and 1,2,4-triazole. Compounds containing a triazole are one of the significant heterocycles that exhibit broad biological activities, such as antimicrobial, analgesic, anti-inflammatory, anticonvulsant, antineoplastic, antimalarial, antiviral, antiproliferative, and anticancer activities. A great quantity of drugs with a triazole structure has been developed and proved, for example, ketoconazole and fluconazole. Given the importance of the triazole scaffold, its synthesis has attracted much attention. This review summarizes the synthetic methods of triazole compounds from various nitrogen sources in the past 20 years.

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“…In the intestines, alpha-glucosidase is an enzyme that converts food polysaccharides into absorbable glucose, which then enters the blood and increases sugar level [ 10 , 11 , 12 ]. Therefore, inhibition of alpha-glucosidase is an effective strategy to control hyperglycemia [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental and Computational Analysis of Newly Synthesized Benzotriazinone Sulfonamides as Alpha-Glucosidase Inhibitors

et al. 2022

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Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, 1H-NMR and 13C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC50 values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.

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A review on synthesis, mechanism of action, and structure-activity relationships of 1,2,3-triazole-based α-glucosidase inhibitors as promising anti-diabetic agents

Cited by 62 publications

References 81 publications

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Synthesis methods of 1,2,3-/1,2,4-triazoles: A review

Experimental and Computational Analysis of Newly Synthesized Benzotriazinone Sulfonamides as Alpha-Glucosidase Inhibitors

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