Synthesis, in vitro α-glucosidase and α-amylase activities and molecular docking study of oxadiazole-sulphonamide hybrid analogues

Ullah, Hayat; Aslam, Muhammad Waseem; Hussain, Amjad; Perviaz, Muhammad

doi:10.1016/j.cdc.2023.101031

Cited by 4 publications

(4 citation statements)

References 49 publications

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“…Despite their therapeutic effectiveness, these well-known inhibitors are unfortunately associated with a wide range of negative side effects. [11,12] Acetazolamide is a strong inhibitor of CA, widely used to regulate fluid secretion, manage specific convulsive disorders, and facilitate diuresis in cases of abnormal fluid retention. [33] However, the administration of this medication may lead to symptoms like nausea, fatigue, and less refreshed.…”

Section: Inhibition Studiesmentioning

confidence: 99%

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In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

Guney,

Aggul,

Erturk

et al. 2023

ChemistrySelect

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In this study, a novel series of sulfonate esters derived from 3‐hydroxyflavone was synthesized and their inhibitory effects on acetylcholinesterase (AChE), α‐glycosidase (AG), and carbonic anhydrase I and II (hCA I and II) enzymes were investigated using experimental and molecular docking analyses. The synthesis involved the reaction of 3‐hydroxyflavone with tosyl chloride, mesytl chloride, β‐naphthylsulfonyl chloride, and 8‐quinolinesulfonyl chloride. The characterization of each compound was confirmed by obtaining 1H NMR, 13C NMR and IR spectra. Furthermore, IC50 and Ki values for the synthesized compounds were calculated and compared to the clinical enzyme inhibitors. Our results showed that the synthesized compounds exhibited inhibition against the targeted enzymes, with Ki values ranging from 1.92 to 4.16 nM for AChE, 32.40 to 55.49 nM for AG, 9.45 to 65.53 nM for hCA I, and 76.62 to 163.33 nM for hCA II. The compound involved quinolinesulfonyl moiety demonstrated especially potent inhibition with IC50 values of 3.96 nM for AChE, 32.40 nM for AG, 9.50 nM for hCA I, and 76.62 nM for hCA II. The docking results aligned well with our experimental findings. The findings have promising implications for the development of novel inhibitors and drug discovery efforts in the future.

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Section: Inhibition Studiesmentioning

confidence: 99%

“…[11] Nonetheless, the effects of AG inhibitors are variable, and many other discovered agents lack practical applicability. [12] Hence, the discovery of new drugs showing better efficacy, making less glucose available for digestion, and reducing postprandial hyperglycemia is necessary.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

Guney,

Aggul,

Erturk

et al. 2023

ChemistrySelect

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“…[21][22][23] Several researches described the synthesis of sulfonamides containing molecules that act as antidiabetics by inhibiting a-glucosidase enzyme. [24][25][26][27][28][29][30] These compounds contain some common structural features namely a p-substituted sulfonamide ring attached to a nitrogen-containing spacer which is consequently attached to phenyl, cyclic, or heterocyclic ring as in compounds A, 30 B 27 and C 28 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Novel sulfonamide derivatives as multitarget antidiabetic agents: design, synthesis, and biological evaluation

Ayoup,

Khaled,

Abdel-Hamid

et al. 2024

RSC Adv.

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“…However, some limitations, in terms of side effects and potency, are also associated with these drugs [13] . This intricacy encourages researchers to keep searching for more promising α‐glucosidase inhibitors with improved safety and efficiency [14–16] . Figure 1 is highlighting some recently reported potent α‐glucosidase inhibitors containing 1,3,4‐oxadiazole ( A–C ) [17–19] and pyrazole ( D–F ) [20–22] molecular systems.…”

Section: Introductiomentioning

confidence: 99%

Synthesis, in vitro α‐Glucosidase Inhibition, DFT Calculations, and Molecular Docking Studies of Some New Substituted 2,5‐Bis(pyrazolyl)‐1,3,4‐oxadiazoles

Chaudhry,

Abdullah,

un‐Nisa

et al. 2024

ChemistrySelect

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A pivotal feature of present research study is the synthesis of some new 2,5‐bis(pyrazolyl)‐1,3,4‐oxadiazoles as promising α‐glucosidase inhibitors. In this regard, a facile reaction scheme was designed to afford 1,3,4‐oxadiazole ring. In search of the most favourable reaction condition, a model reaction was first carried out between 1,3‐diphenyl‐1H‐pyrazole‐4‐carbohydrazide (3) and 1,3‐diphenyl‐1H‐pyrazole‐4‐carboxylic acid (4 a) using phosphorous oxychloride (POCl3). The results emanated from this model reaction were utilized to prepare other derivatives to highlight the scope of current synthetic approach and the structures of the prepared molecules were characterized from spectroscopic techniques. These derivatives were further investigated for their α‐glucosidase inhibitory potentials. 2,5‐Bis(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐1,3,4‐oxadiazole (5 a) and 2‐(3‐(4‐bromophenyl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐5‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)‐1,3,4‐oxadiazole (5 c) displayed strong in vitro inhibitory activities with IC50 73.1±1.13 μM and IC50 87.3±1.12 μM respectively with least toxicity profiles. Molecular docking and computational studies including geometry optimization of synthesized molecular systems, calculations of their orbital energies, and molecular electrostatic potential (MEP) surface maps further helped to establish structural and electronic properties contributing towards their bioactivity. The electrophilicity index significantly quantifies the biological activity. The experimental and computational data altogether facilitated in understanding the therapeutic attributes of these versatile scaffolds in relation to their α‐glucosidase inhibition.

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Synthesis, in vitro α-glucosidase and α-amylase activities and molecular docking study of oxadiazole-sulphonamide hybrid analogues

Cited by 4 publications

References 49 publications

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

In Vitro and in Silico Studies of 3‐Hydroxyflavone‐Based Sulfonate Esters: Potent Acetylcholinesterase, Carbonic Anhydrase and α‐Glycosidase Inhibitors

Novel sulfonamide derivatives as multitarget antidiabetic agents: design, synthesis, and biological evaluation

Synthesis, in vitro α‐Glucosidase Inhibition, DFT Calculations, and Molecular Docking Studies of Some New Substituted 2,5‐Bis(pyrazolyl)‐1,3,4‐oxadiazoles

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