Design, synthesis, biological evaluation, and docking study of chromone-based phenylhydrazone and benzoylhydrazone derivatives as antidiabetic agents targeting α‐glucosidase

Fan, Meiyan; Yang, Wei; Liu, Lin; Peng, Zhiyuan; He, Yan; Wang, Guangcheng

doi:10.1016/j.bioorg.2023.106384

Cited by 17 publications

(4 citation statements)

References 48 publications

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“…The crystal was stacked in the Z isomer structure as also compound 1 a. The selected bond angles range between 120.15(16)°and 128.90 (19)°. In the crystal packing structures of both compounds, there are some intra-and inter-molecular hydrogen bonding interactions are also observed.…”

Section: Structural Analysismentioning

confidence: 99%

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Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

et al. 2023

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The nine new imidazole-hydrazone derivatives of Schiff base were synthesized from the condensation reactions of 1-methyl-1H-imidazole-2-carbaldehyde with various substitutedhydrazide derivatives. Structures of the final compounds (1 a-1 i) were characterized by using 1 H NMR, 13 C NMR spectroscopic techniques, elemental analysis, and crystal X-ray diffraction. The in vitro carbonic anhydrase I and II potentials of these synthesized were evaluated. The result suggests that compound 1 a, a 4-methoxy substituted analog with an IC 50 of 0.949 μM, was found to have the most potent hCA I inhibitory activity. Compounds 1 c, 1 d, and 1 h were the most potent compounds on hCA II with IC 50 values of 3.330, 4.454, and 5.66 μM, respectively. All compounds were examined for their cytotoxicity towards human colorectal adenocarcinoma cell (HT29) and rat glioma cell line (C6) compared to mouse fibroblast normal cell line (L929) using the MTT assay method. The compounds 1 a, 1 d, and 1 i exhibited significant antiproliferative activity with less toxicity to a health cell line. Consequently, compound 1 a could be the potential lead for emerging selective cytotoxic compounds directing hCA I. Compound 1 d could be the potential lead for emerging selective cytotoxic compounds directing hCA II.

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Section: Structural Analysismentioning

confidence: 99%

“…[16] This discovery has had a substantial impact on medical chemistry. These compounds' acetylcholinesterases, [17] anticancer, [18] α-glucosidase, [19] antitubercular, [20] anti-mitotic, [21] antimicrobial, [22] and antifungal [23] properties are also of great interest.…”

Section: Introductionmentioning

confidence: 99%

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

et al. 2023

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“…[28] Additionally, both natural and synthetic chromone derivatives have demonstrated noteworthy inhibitory activities against α-glucosidase, suggesting their relevance in addressing diabetes-related concerns. [29][30][31][32][33] Furthermore, the combination of chromone derivatives with different moieties has been reported to yield significant antidiabetic effects, as shown in Figure 1. The collective evidence from previous studies indicates that chromone holds promise as a readily available pharmacophoric fragment in the search for and development of potential α-glucosidase inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

Alharthy,

Khalid,

Fatima

et al. 2024

Archiv der Pharmazie

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Diabetes is a serious metabolic disorder affecting individuals of all age groups and prevails globally due to the failure of previous treatments. This study aims to address the most prevalent form of type 2 diabetes mellitus (T2DM) by reporting on the design, synthesis, and in vitro as well as in silico evaluation of chromone‐based thiosemicarbazones as potential α‐glucosidase inhibitors. In vitro experiments showed that the tested compounds were significantly more potent than the standard acarbose, with the lead compound 3n exhibiting an IC50 value of 0.40 ± 0.02 μM, ~2183‐fold higher than acarbose having an IC50 of 873.34 ± 1.67 μM. A kinetic mechanism analysis demonstrated that compound 3n exhibited reversible inhibition of α‐glucosidase. To gain deeper insights, in silico molecular docking, pharmacokinetics, and molecular dynamics simulations were conducted for the investigation of the interactions, orientation, stability, and conformation of the synthesized compounds within the active pocket of α‐glucosidase.

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“…Up to now, increasingly more α-glucosidase inhibitors have been developed, but only a few inhibitors are clinically used for the treatment of type 2 diabetes, such as acarbose, voglibose, and miglitol [ 11 , 12 , 13 ]. Moreover, long-term use of these drugs also leads to some gastrointestinal side effects, including diarrhea and flatulence [ 14 , 15 ]. This situation has encouraged the authors to develop more efficient and safer α-glucosidase inhibitors [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

Liu

et al. 2023

Molecules

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To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1–20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.

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Design, synthesis, biological evaluation, and docking study of chromone-based phenylhydrazone and benzoylhydrazone derivatives as antidiabetic agents targeting α‐glucosidase

Cited by 17 publications

References 48 publications

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

Synthesis of the chromone‐thiosemicarbazone scaffold as promising α‐glucosidase inhibitors: An in vitro and in silico approach toward antidiabetic drug design

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

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