Synthesis of Novel N-Methylmorpholine-Substituted Benzimidazolium Salts as Potential α-Glucosidase Inhibitors

Khan, Imran; Saddique, Furqan Ahmad; Aslam, Sana; Ashfaq, Usman Ali; Ahmad, Matloob; Al‐Hussain, Sami A.; Zaki, Magdi E. A.

doi:10.3390/molecules27186012

Cited by 5 publications

(4 citation statements)

References 45 publications

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“…It is worth noting that the majority of the analogs were found to have good to moderately active IC 50 values ranging from 18.65 ± 0.23 to 28.33 ± 0.02 µM for α-amylase inhibition and with the IC 50 values ranging from 17.47 ± 0.03 to 29.01 ± 0.12 µM for α-glucosidase inhibition except compounds 3a , 3b , and 3h . The inhibitory activities of α-amylase and α-glucosidase, according to Table 3 , revealed that the tested compounds in the current study demonstrate higher activities than those reported in previous studies [ 47 , 72 ].…”

Section: Resultscontrasting

confidence: 46%

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity

et al. 2023

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A novel series of benzimidazole ureas 3a–h were elaborated using 2-(1H-benzoimidazol-2-yl) aniline 1 and the appropriate isocyanates 2a–h. The antioxidant and possible antidiabetic activities of the target benzimidazole-ureas 3a–h were evaluated. Almost all compounds 3a–h displayed strong to moderate antioxidant activities. When tested using the three antioxidant techniques, TAC, FRAP, and MCA, compounds 3b and 3c exhibited marked activity. The most active antioxidant compound in this family was compound 3g, which had excellent activity using four different methods: TAC, FRAP, DPPH-SA, and MCA. In vitro antidiabetic assays against α-amylase and α-glucosidase enzymes revealed that the majority of the compounds tested had good to moderate activity. The most favorable results were obtained with compounds 3c, 3e, and 3g, and analysis revealed that compounds 3c (IC50 = 18.65 ± 0.23 μM), 3e (IC50 = 20.7 ± 0.06 μM), and 3g (IC50 = 22.33 ± 0.12 μM) had good α-amylase inhibitory potential comparable to standard acarbose (IC50 = 14.21 ± 0.06 μM). Furthermore, the inhibitory effect of 3c (IC50 = 17.47 ± 0.03 μM), 3e (IC50 = 21.97 ± 0.19 μM), and 3g (IC50 = 23.01 ± 0.12 μM) on α-glucosidase was also comparable to acarbose (IC50 = 15.41 ± 0.32 μM). According to in silico molecular docking studies, compounds 3a–h had considerable affinity for the active sites of human lysosomal acid α-glucosidase (HLAG) and pancreatic α-amylase (HPA), indicating that the majority of the examined compounds had potential anti-hyperglycemic action.

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Section: Resultscontrasting

confidence: 46%

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity

et al. 2023

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“…The most effective inhibitors inhibited the enzyme by 63% and 99%; moreover, these compounds showed antioxidant activity [17]. Khan et al [18] also synthesized a series of 1-benzyl-3-((2-substitutedphenyl)amino)-2-oxoethyl)-2-(morpholinomethyl)-1H-benzimidazol-3-ium chloride (Figure 7) and checked them for α-glucosidase inhibitory activity in vitro. The compound 1-benzyl-3-( 2…”

Section: Morpholine Derivatives As Antidiabetic Drugsmentioning

confidence: 99%

“…The series of 4-(5-fluoro-2-substituted-1H-benzimidazol-6-yl)morpholine derivatives showed remarkable α-glucosidase inhibitory potentials [19]. A compound shown in Figure 8, which has a methoxy group on the phenyl ring, was found to be the most active Khan et al [18] also synthesized a series of 1-benzyl-3-((2-substitutedphenyl)amino)-2oxoethyl)-2-(morpholinomethyl)-1H-benzimidazol-3-ium chloride (Figure 7) and checked them for α-glucosidase inhibitory activity in vitro. The compound 1-benzyl-3-( 2…”

Section: Morpholine Derivatives As Antidiabetic Drugsmentioning

confidence: 99%

Morpholine, Piperazine, and Piperidine Derivatives as Antidiabetic Agents

Zolotareva,

Zazybin,

Dauletbakov

et al. 2024

Molecules

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Diabetes mellitus is a severe endocrine disease that affects more and more people every year. Modern medical chemistry sets itself the task of finding effective and safe drugs against diabetes. This review provides an overview of potential antidiabetic drugs based on three heterocyclic compounds, namely morpholine, piperazine, and piperidine. Studies have shown that compounds containing their moieties can be quite effective in vitro and in vivo for the treatment of diabetes and its consequences.

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“…The coupling of two or more pharmacologically important scaffolds is a diverse approach that can produce hybrid molecules with enhanced biological activity. In continuation of our previous research work dealing with the development of various enzyme inhibitors, for example, α-amylase and α-glucosidase inhibitors ( Khan et al, 2021 ; Khan et al, 2022 ; Saddique et al, 2022 ), we herein report a novel series of pyridine-based piperazines as potent urease inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

Akash,

Zaib,

Ahmad

et al. 2024

Front. Chem.

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Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 µM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 µM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of −8.0 (5b) and −8.1 (7e) kcal/mol. The binding energy of thiourea was −2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 µM and −6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease.

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Synthesis of Novel N-Methylmorpholine-Substituted Benzimidazolium Salts as Potential α-Glucosidase Inhibitors

Cited by 5 publications

References 45 publications

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity

Synthesis, Molecular Docking, and Bioactivity Study of Novel Hybrid Benzimidazole Urea Derivatives: A Promising α-Amylase and α-Glucosidase Inhibitor Candidate with Antioxidant Activity

Morpholine, Piperazine, and Piperidine Derivatives as Antidiabetic Agents

Synthesis and biological evaluation of pyridylpiperazine hybrid derivatives as urease inhibitors

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