Synthesis, crystal structure and Hirshfeld Surface analysis of benzamide derivatives of thiourea as potent inhibitors of α-glucosidase in-vitro

Akhter, Sidra; Ullah, Saeed; Yousuf, Sammer; Atia-tul-Wahab, *; Siddiqui, Hamid Latif; Choudhary, Muhammad Iqbal

doi:10.1016/j.bioorg.2020.104531

Cited by 27 publications

(9 citation statements)

References 24 publications

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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%

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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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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“…A fundamental treatment method used to overcome hyperglycemia is to reduce carbohydrate digestion and absorption, which provides an insight into the important role of α-glucosidase. As a result, novel AGIs with fewer side effects are urgently needed, in contrast to the currently existing clinical AGIs, such as acarbose, voglibose, and miglitol [ 32 , 33 ]. Recently, it was reported in the literature that both 1 H -1,2,3-triazole and BAs are active pharmacophores of α-glucosidase inhibitors [ 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies

et al. 2023

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A series of 24 new 1H-1,2,3-triazole hybrids of 3-O-acetyl-11-keto-β-boswellic acid (β-AKBA (1)) and 11-keto-β-boswellic acid (β-KBA (2)) was designed and synthesized by employing “click” chemistry in a highly efficient manner. The 1,3-dipolar cycloaddition reaction between β-AKBA-propargyl ester intermediate 3 or β-KBA-propargyl ester intermediate 4 with substituted aromatic azides 5a–5k in the presence of copper iodide (CuI) and Hünig’s base furnished the desired products—1H-1,2,3-triazole hybrids of β-AKBA (6a–6k) and β-KBA (7a–7k)—in high yields. All new synthesized compounds were characterized by 1H-, 13C-NMR spectroscopy, and HR-ESI-MS spectrometry. Furthermore, their α-glucosidase-inhibitory activity was evaluated in vitro. Interestingly, the results obtained from the α-glucosidase-inhibitory assay revealed that all the synthesized derivatives are highly potent inhibitors, with IC50 values ranging from 0.22 to 5.32 µM. Among all the compounds, 6f, 7h, 6j, 6h, 6g, 6c, 6k, 7g, and 7k exhibited exceptional inhibitory potency and were found to be several times more potent than the parent compounds 1 and 2, as well as standard acarbose. Kinetic studies of compounds 6g and 7h exhibited competitive and mixed types of inhibition, with ki values of 0.84 ± 0.007 and 1.18 ± 0.0012 µM, respectively. Molecular docking was carried out to investigate the binding modes of these compounds with α-glucosidase. The molecular docking interactions indicated that that all compounds are well fitted in the active site of α-glucosidase, where His280, Gln279, Asp215, His351, Arg442, and Arg315 mainly stabilize the binding of these compounds. The current study demonstrates the usefulness of incorporating a 1H-1,2,3-triazole moiety into the medicinally fascinating boswellic acids skeleton.

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“…The amyloid cascade hypothesis 1 suggests that the consequent accumulation of Aβ peptides mediates the pathogenesis of AD through synaptic injury, gliosis, and NFTs. Amyloid beta loads are associated positively with clinical cognitive severity and faster cognitive decline in people with subjective memory impairment (SMI), 2 mild cognitive impairment (MCI), 3 and early AD.…”

Section: Introductionmentioning

confidence: 99%

“…Thiourea functional groups have numerous pharmacological activities such as antidiabetic, antibacterial, antifungal, antiviral, anticancer, anticonvulsant, antidiabetic (1)(2)(3). Thioureas play an important role in the regulation of various pharmacological activities by increasing potency and selectivity or by modulating of physicochemical properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Biological Evaluation of Novel Thiourea Derivatives

Tok

Çakir

Çam

et al. 2022

Clinical and Experimental Health Sciences

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Objective: A new series of 4-[3-(substitutedphenyl)thioureido]-N-(6-chloropyrazin-2-yl)benzenesulfonamide were synthesized from sulfaclozine. Methods: All compounds were characterized by IR, 1H-NMR spectroscopic methods and elemental analysis. In addition to the antioxidant activity of the synthesis series, enzyme inhibition activities such as anticholinesterase, tyrosinase, α-amylase and α-glycosidase were determined for the first time in this study. Results: According to these biological activity test results, compound 2a in the DPPH, 2c in the ABTS˙+ assay exhibited more antioxidant activity than reference standard. All thiourea derivatives demonstrated good BChE inhibitory activity than galantamine. Among the compounds, 2e and 2f showed the best tyrosinase enzyme inhibition activity, while 2g had the best α-amylase and α-glucosidase enzyme inhibition activity. In addition, we evaluated the druglikeness properties of compounds and their oral bioavailability were also found to be high. Conclusion: Thiourea derivatives exhibited remarkable antioxidant activity and enzyme inhibition activity against tyrosinase, cholinesterase, α-amylase and α-glucosidase.

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Synthesis, crystal structure and Hirshfeld Surface analysis of benzamide derivatives of thiourea as potent inhibitors of α-glucosidase in-vitro

Cited by 27 publications

References 24 publications

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

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

Discovery of New Boswellic Acid Hybrid 1H-1,2,3-Triazoles for Diabetic Management: In Vitro and In Silico Studies

Synthesis, Characterization and Biological Evaluation of Novel Thiourea Derivatives

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