New β-carboline derivatives as potential α-glucosidase inhibitor: Synthesis and biological activity evaluation

Lin, Jenshan; Xiao, Di; Lu, Li; Liang, Bingwen; Xiong, Zhuang; Xu, Xuetao

doi:10.1016/j.molstruc.2023.135279

Cited by 28 publications

(15 citation statements)

References 40 publications

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“…Figure 3 A displays the relationship between the tyrosinase concentration with residual enzyme activity under compound c27 (0~4 μM), which shows straight lines passing through the origin with different slopes. Therefore, compound c27 was identified as a reversible inhibitor [ 49 , 50 ]. Figure 3 B shows the Lineweaver–Burk plots of substrate concentration and residual enzyme activity under compound c27 (0~4 μM).…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Min

Zheng

et al. 2023

Molecules

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Tyrosinase plays crucial roles in mediating the production of melanin pigment; thus, its inhibitors could be useful in preventing melanin-related diseases. To find potential tyrosinase inhibitors, a series of cinnamic acid–eugenol esters (c1~c29) was synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, HRMS, and FT-IR, respectively. The biological evaluation results showed that all compounds c1~c29 exhibited definite tyrosinase inhibitory activity; especially, compound c27 was the strongest tyrosinase inhibitor (IC50: 3.07 ± 0.26 μM), being ~4.6-fold stronger than the positive control, kojic acid (IC50: 14.15 ± 0.46 μM). Inhibition kinetic studies validated compound c27 as a reversible mixed-type inhibitor against tyrosinase. Three-dimensional fluorescence and circular dichroism (CD) spectra results indicated that compound c27 could change the conformation and secondary structure of tyrosinase. Fluorescence-quenching results showed that compound c27 quenched tyrosinase fluorescence in the static manner with one binding site. Molecular docking results also revealed the binding interactions between compound c27 and tyrosinase. Therefore, cinnamic acid–eugenol esters, especially c27, could be used as lead compounds to find potential tyrosinase inhibitors.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Min

Zheng

et al. 2023

Molecules

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“…Molecular docking was performed to simulate the binding of MY15–17 with PTP1B using SYBYL. , The structure of PTP1B (PDB: 1XBO) was optimized by the procedure, including removing water, adding hydrogen, adding charge, fixing side chains, and generating the active pocket in automatic mode. The protomol frid dimensions data ( x , y , z ) was 27 × 27 × 25.…”

Section: Methodsmentioning

confidence: 99%

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

Li,

Min

et al. 2024

J. Med. Chem.

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Forty-one 1,3,4-thiadiazolyl-containing thiazolidine-2,4dione derivatives (MY1−41) were designed and synthesized as protein tyrosine phosphatase 1B (PTP1B) inhibitors with activity against diabetes mellitus (DM). All synthesized compounds (MY1−41) presented potential PTP1B inhibitory activities, with half-maximal inhibitory concentration (IC 50 ) values ranging from 0.41 ± 0.05 to 4.68 ± 0.61 μM, compared with that of the positive control lithocholic acid (IC 50 = 9.62 ± 0.14 μM). The most potent compound, MY17 (IC 50 = 0.41 ± 0.05 μM), was a reversible, noncompetitive inhibitor of PTP1B. Circular dichroism spectroscopy and molecular docking were employed to analyze the binding interaction between MY17 and PTP1B. In HepG2 cells, MY17 treatment could alleviate palmitic acid (PA)-induced insulin resistance by upregulating the expression of phosphorylated insulin receptor substrate and protein kinase B. In vivo, oral administration of MY17 could reduce the fasting blood glucose level and improve glucose tolerance and dyslipidemia in mice suffering from DM.

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“…Molecular docking between compounds 9 , 11 , 13 , 18 , and 19 and α-glucosidase was conducted using SYBYL software [ 41 , 42 , 43 ]. The homology model of α-glucosidase had been built in our previous works.…”

Section: Methodsmentioning

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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New β-carboline derivatives as potential α-glucosidase inhibitor: Synthesis and biological activity evaluation

Cited by 28 publications

References 40 publications

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Identification of 1,3,4-Thiadiazolyl-Containing Thiazolidine-2,4-dione Derivatives as Novel PTP1B Inhibitors with Antidiabetic Activity

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

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