Phenoxy pendant isatins as potent α-glucosidase inhibitors: reciprocal carbonyl⋯carbonyl interactions, antiparallel π⋯π stacking driven solid state self-assembly and biological evaluation

Mehreen, Saba; Zia, Mehwash; Khan, Ajmal; Hussain, Javid; Ullah, Saeed; Anwar, Muhammad U.; Al‐Harrasi, Ahmed; Naseer, Muhammad Moazzam

doi:10.1039/d2ra03307k

Cited by 23 publications

(12 citation statements)

References 77 publications

(96 reference statements)

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“…Several therapeutic approaches of diabetes are available, but α-glucosidase inhibitors (AGIs), has been considered a precise and specific strategy for the management of type II diabetes mellitus. AGIs, have been considered a valuable approach because these AGIs slow down the catalytic activity of carbohydrates digestive enzyme α -glucosidase 10 , 11 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Pasha

Khan

Ullah

et al. 2023

Sci Rep

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Type II diabetes mellitus (T2DM) is a global health issue with high rate of prevalence. The inhibition of α-glucosidase enzyme has prime importance in the management of T2DM. This study was established to synthesize Schiff bases of 1,3-dipheny urea (3a–y) and to investigate their in vitro anti-diabetic capability via inhibiting α-glucosidase, a key player in the catabolism of carbohydrates. The structures of all compounds were confirmed through various techniques including, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and mass-spectrometry (MS) methods. Interestingly all these compounds displayed potent inhibition IC50 values in range of 2.14–115 µM as compared to acarbose used as control. Additionally, all the compounds were docked at the active site of α-glucosidase to predict their mode of binding. The docking results indicates that Glu277 and Asn350 play important role in the stabilization of these compounds in the active site of enzyme. These molecules showed excellent predicted pharmacokinetics, physicochemical and drug-likeness profile. The anti-diabetic potential of these molecules signifies their medical importance and provide insights into prospective therapeutic options for the treatment of T2DM.

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Section: Introductionmentioning

confidence: 99%

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Pasha

Khan

Ullah

et al. 2023

Sci Rep

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“…In contrast to other hypoglycemic agents that regulate certain biochemical processes, these inhibitors act locally in the human intestine . However, the clinical uses of these are associated with side effects such as abdominal discomfort, diarrhea, and flatulence. − Therefore, synthesis of new α-glucosidase inhibitors with no or minimal side effects is still a reasonable need.…”

Section: Introductionmentioning

confidence: 99%

“… 27 However, the clinical uses of these are associated with side effects such as abdominal discomfort, diarrhea, and flatulence. 28 − 30 Therefore, synthesis of new α-glucosidase inhibitors with no or minimal side effects is still a reasonable need.…”

Section: Introductionmentioning

confidence: 99%

Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes

et al. 2023

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Polyhydroquinoline derivatives (1-15) were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds (1-15) were deduced through different spectroscopic techniques such as 1H NMR, 13C NMR, and HR–ESI–MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC50 = 0.56 ± 0.01 μM), 10 (IC50 = 0.94 ± 0.01 μM), 4 (IC50 = 1.47 ± 0.01 μM), 2 (IC50 = 2.20 ± 0.03 μM), 6 (IC50 = 2.20 ± 0.03 μM), 12 (IC50 = 2.22 ± 0.07 μM), 7 (IC50 = 2.76 ± 0.04 μM), 9 (IC50 = 2.78 ± 0.03 μM), and 3 (IC50 = 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (8, 5, 14, 15, and 13) showed significant α-glucosidase inhibitory potential with IC50 values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 μM, respectively. Among the synthesized series, two compounds, i.e., 11 and 10, showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug “acarbose” (IC50 = 873.34 ± 1.67 μM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results.

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“…Recently, it was shown that aryl-substituted phenoxy-acetamide scaffolds were reported as potent α-glucosidase inhibitors. C=O moiety of acetamide as the key skeletons anchoring can stabilize α-helices, β-sheets, and other secondary structures of biological macromolecules through participation in various forms of interaction including hydrogen bonding, nucleophile–carbonyl, carbonyl–carbonyl (CO/CO) interaction [ 22 ]. Assessments on diphenylimidazole core attached to the various N-aryl acetamides (Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and bioactivities evaluation of quinazolin-4(3H)-one derivatives as α-glucosidase inhibitors

et al. 2022

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The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a–r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus.

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Phenoxy pendant isatins as potent α-glucosidase inhibitors: reciprocal carbonyl⋯carbonyl interactions, antiparallel π⋯π stacking driven solid state self-assembly and biological evaluation

Abstract: Carbonyl–carbonyl (CO⋯CO) interactions are recently explored noncovalent interactions of significant interest owing to their role in the stability of biomacromolecules.

Cited by 23 publications

References 77 publications

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Synthesis of new diphenyl urea-clubbed imine analogs and its Implications in diabetic management through in vitro and in silico approaches

Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes

Synthesis and bioactivities evaluation of quinazolin-4(3H)-one derivatives as α-glucosidase inhibitors

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