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Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies.

ABSTRACT: A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a-m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a-m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC₅₀ range: 0.64 ± 0.05 μM to 343.10 ± 1.62 μM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC₅₀: 0.64 ± 0.05 μM) followed by 7d (IC₅₀: 5.34 ± 0.16 μM), 7f (IC₅₀: 6.46 ± 0.30 μM), 7g (IC₅₀: 8.62 ± 0.19 μM), 7c (IC₅₀: 9.84 ± 0.08 μM), 7m (IC₅₀: 11.09 ± 0.79 μM), 7a (IC₅₀: 11.84 ± 0.26 μM), 7e (IC₅₀: 16.38 ± 0.53 μM), 7j (IC₅₀: 18.65 ± 0.74 μM), 7h (IC₅₀: 20.73 ± 0.59 μM), 7b (IC₅₀: 27.26 ± 0.30 μM), 7k (70.28 ± 1.52 μM) and finally 7l (IC₅₀: 343.10 ± 1.62 μM). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings.

SUBMITTER: Ali S

PROVIDER: S-EPMC9730482 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies.

Ali Sardar S Ali Mumtaz M Khan Ajmal A Ullah Saeed S Waqas Muhammad M Al-Harrasi Ahmed A Latif Abdul A Ahmad Manzoor M Saadiq Muhammad M

ACS omega 20221123 48

A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a-m provided access to ...[more]

PMID: 36506132

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Project description:IntroductionThe current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays.MethodsIn this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal (Compound 2) were synthesized using Michael addition. Both the compounds, ie, 1 and 2 were evaluated for in-vitro acetylcholinesterase (AChE), butyrylctcholinesterase (BChE), antioxidant, and α-glucosidase inhibitory potentials. Furthermore, molecular docking was performed using Molecular Operating Environment (MOE) to explore the binding mode of both the compounds against different enzymes. Lineweaver-Burk plots of enzyme inhibitions representing the reciprocal of initial enzyme velocity versus the reciprocal of substrate concentration in the presence of synthesized compounds and standard drugs were constructed using Michaelis-Menten kinetics.ResultsIn AChE inhibitory assay, compounds 1 and 2 exhibited IC50 of 343.45 and 422.98 µM, respectively, against AChE enzyme. Similarly, both the compounds showed IC50 of 276.86 and 357.91 µM, respectively, against BChE enzyme. Compounds 1 and 2 displayed IC50 of 157.71 and 471.79 µM against α-glucosidase enzyme, respectively. In a similar pattern, compound 1 exhibited to be more potent as compared to compound 2 in all the three antioxidant assays. Compound 1 exhibited IC50 values of 297.98, 332.94, and 825.92 µM against DPPH, ABTS, and H2O2 free radicals, respectively. Molecular docking showed a triple fold in the AChE and BChE activity for compound 1 compared with compound 2. The compound 1 revealed good interaction against both the AChE and BChE enzymes which revealed the high potency of this compound compared to compound 2.ConclusionBoth succinimide derivatives exhibited considerable inhibitory activities against cholinesterases and α-glucosidase enzymes. Of these two, compound 1 revealed to be more potent against all the in-vitro targets which was supported by molecular docking with the lowest binding energies. Moreover, compound 1 also proved to have antiradical properties.

Dataset Information

Novel 5-(Arylideneamino)-1H-Benzo[d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies.

Publications

Novel 5-(Arylideneamino)-1<i>H</i>-Benzo[<i>d</i>]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition, and Molecular Docking Studies.

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