Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics

Shahzad, Danish; Saeed, Aamer; Larik, Fayaz Ali; Channar, Pervaiz Ali; Abbas, Qamar; Alajmi, Mohamed F.; Arshad, Ifzan; Erben, Mauricio F.; Hassan, Mubashir; Raza, Hussain; El‐Seedi, Hesham R.

doi:10.3390/molecules24081511

Cited by 46 publications

(28 citation statements)

References 45 publications

(49 reference statements)

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“…Shahzad et al synthesised a series of symmetrical salicylaldehyde-bishydrazine azo molecules. The high activity of compounds is mainly caused by hydrogen bonds 24 , which were the same with us.…”

Section: Docking Studysupporting

confidence: 70%

Synthesis,in vitroinhibitory activity, kinetic study and molecular docking of novelN-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors

Lin

Zeng

Chen

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of novel N -alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC 50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC 50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43 , 40 , and 34 were all competitive inhibitors on α-glucosidase with K i of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π–π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π–π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.

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Section: Docking Studysupporting

confidence: 70%

Synthesis,in vitroinhibitory activity, kinetic study and molecular docking of novelN-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors

Lin

Zeng

Chen

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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show abstract

“…After completion of the reaction, the mixture was cooled to room temperature, the precipitated solid was isolated by filtration, all products were recrystallized from hot ethanol. Physical and spectral data of bis aryl hydrazide derivatives are given below [ 51 – 53 ].…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

et al. 2021

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A series of symmetrical azine derivatives containing different substituted benzyl moieties were designed, synthesized, and evaluated for their inhibitory activity against tyrosinase. The results showed that compounds 3e, 3f, 3h, 3i, 3j, and 3k possess effective tyrosinase inhibition with IC50 values ranging from 7.30 μM to 62.60 μM. Particularly, compounds 3f displayed around three-fold improvement in the potency (IC50 = 7.30 ± 1.15 μM) compared to that of kojic acid (IC50 = 20.24 ± 2.28 μM) as the positive control. Kinetic study of compound 3f confirmed uncompetitive inhibitory activity towards tyrosinase indicating that it can bind to enzyme–substrate complex. Next, molecular docking analysis was performed to study the interactions and binding mode of the most potent compound 3f in the tyrosinase active site. Besides, the cytotoxicity of 3f, as well as its potency to reduce the melanin content were also measured on invasive melanoma B16F10 cell line. Also, 3f exhibited above 82% cell viability in the A375 cell line at 10 µM. Consequently, compounds 3f could be introduced as a potent tyrosinase inhibitor that might be a promising candidate in the cosmetics, medicine, and food industry.

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“…Then, 20 μL of the substrate solution was added, and absorbance was measured at 405 nm. The reaction was measured 10 times every 2 min (20 min) [25,26] . Acarbose was used as the positive control.…”

Section: Methodsmentioning

confidence: 99%

A New Apotirucallane from Walsura trichostemon Leaves and Its Antibacterial and α‐Glucosidase Inhibitory Activities

Suchaichit

Pitchuanchom

Kanokmedhakul

et al. 2021

Chemistry & Biodiversity

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Phytochemical investigation of Walsura trichostemon leaves led to the isolation of a new apotirucallane‐type triterpenoid, 11,25‐dideacetyl‐16‐hydroxytrichostemonate (1), along with two known apotirucallane‐type triterpenoids (2 and 3), two known tirucallane‐type triterpenes (4 and 5), and two known steroids (6 and 7). Their structures were identified by intensive analysis of 1D and 2D nuclear magnetic resonance, infrared, and mass spectrometry data, which were compared with data reported in the literature. Compounds 2, 3, and 5 exhibited moderate antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) value: 64 μg/mL), and compound 4 showed weak antibacterial activity against P. aeruginosa (MIC: 128 μg/mL). Furthermore, compound 5 displayed activity against Bacillus cereus (MIC: 64 μg/mL). In addition, compound 4 showed stronger α‐glucosidase inhibitory activity than the control, acarbose. The active compound 4 was subjected to molecular docking experiments using AutoDock4 and revealed precise interactions with the active gorge of the enzyme through hydrogen bonding, supporting the in vitro results.

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Novel C-2 Symmetric Molecules as α-Glucosidase and α-Amylase Inhibitors: Design, Synthesis, Kinetic Evaluation, Molecular Docking and Pharmacokinetics

Cited by 46 publications

References 45 publications

Synthesis,in vitroinhibitory activity, kinetic study and molecular docking of novelN-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors

Synthesis,in vitroinhibitory activity, kinetic study and molecular docking of novelN-alkyl–deoxynojirimycin derivatives as potential α-glucosidase inhibitors

Design, synthesis, and biological evaluation of symmetrical azine derivatives as novel tyrosinase inhibitors

A New Apotirucallane from Walsura trichostemon Leaves and Its Antibacterial and α‐Glucosidase Inhibitory Activities

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