Synthesis of indole-based-thiadiazole derivatives as a potent inhibitor of α-glucosidase enzyme along with in silico study

Alomari, Munther; Taha, Muhammad; Selvaraj, Manikandan; Iqbal, Naveed; Chigurupati, Sridevi; Hussain, Shafqat; Uddin, Nizam; Almandil, Noor B.; Nawaz, Muhammad; Farooq, Rai Khalid; Khan, Khalid Mohammed

doi:10.1016/j.bioorg.2021.104638

Cited by 38 publications

(21 citation statements)

References 47 publications

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“…Isatin (1) was used as basic precursor to prepare isatoic anhydride (2) by the oxidation reaction with hydrogen peroxide in the presence of formic acid. Compound 2 was treated with sulfanilic acid to form 4-(2-aminobenzamido)benzenesulfonic acid (3) that was subjected to cyclization with the help of nitrous acid to 4-(4-Oxobenzo [1,2,3]triazin-3(4H)-yl)benzenesulfonic acid (4). Then triazin-based sulfonic acid (4) was directly converted to series of sulfonamide compounds 5a-m (Scheme 1) by using TCT:DMF adduct.…”

Section: Chemistrymentioning

confidence: 99%

“…The sulfonamides based on heterocyclic systems are emerging as potent αglucosidase inhibitors. Various sulfonamide molecules based on indole [2], chalcone [3], Celebrex [4], sulfaguanidine [5], and quinoline [6], have demonstrated effective α-glucosidase inhibition activity as compared to the available drug, acrobase.…”

Section: Introductionmentioning

confidence: 99%

“…In this research work, the synthesis of N-alkyl / aryl-4-(4-oxobenzo [1,2,3]triazin-3(4H)yl)benzenesulfonamides were achieved through one pot, simple and low cost methodology under mild conditions. The most common method for sulfonamide synthesis is by the reaction of sulfonyl chloride and amine under basic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 1,2,3-benzotriazin-4(3H)-one derivatives as α-glucosidase inhibitor and their in-silico study

et al. 2022

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α-Glucosidase inhibition is considered as an effective strategy for the treatment of diabetes mellitus.Currently, three α-glucosidase inhibitors are being used as drugs; Acarbose, Voglibose and Miglitol. The side effects of these drugs are forcing researchers to search for new and effective molecules. In this research work, novel 1,2,3-benzotriazin-4(3H)-one sulfonamides were synthesized and investigated for their α-glucosidase inhibition activity. TCT: DMF adduct have been utilized for the direct synthesis of targeted sulfonamides. All reactions were performed at room temperature under mild conditions. In-vitro enzyme inhibition studies led us to discover many potent inhibitors demonstrating good to excellent activity. The compound 5c with dimethyl substituent was found to be more potent inhibitor than acarbose with the IC 50 value of 29.75±0.14 μM. Compounds 5a, 5b, 5d, 5e, 5f and 5m showed good inhibition results with IC 50 value 31.97±0.03, 33.24±0.01, 33.76±1.05, 35.98±0.03, 30.87±0.51 and 37.24±0.04 µM respectively. Further structure activity relationship was analyzed by molecular docking studies.

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Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of 1,2,3-benzotriazin-4(3H)-one derivatives as α-glucosidase inhibitor and their in-silico study

et al. 2022

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“…In the last years, a variety of synthetic and natural α-glucosidase inhibitors have been developed 11 – 16 . Most of the potent inhibitors contain heterocyclic compounds 11 and coumarins 17 , thiadiazoles 18 , imidazoles and benzimidazoles 19 , 20 , pyrazoles-benzofurans 21 , oxindoles 22 , and isatins 16 are examples of synthetic α-glucosidase inhibitors. Further, 1,2,3-triazole based compounds were recently introduced as potent α-glucosidase inhibitors 12 , 16 , 23 , 24 .…”

Section: Introductionmentioning

confidence: 99%

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Iraji

Shareghi-Brojeni

Mojtabavi

et al. 2022

Sci Rep

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In this work, a novel series of cyanoacetohydrazide linked to 1,2,3-triazoles (9a–n) were designed and synthesized to be evaluated for their anti-α-glucosidase activity, focusing on the fact that α-glucosidase inhibitors have played a significant role in the management of type 2 diabetes mellitus. All synthesized compounds except 9a exhibited excellent inhibitory potential, with IC50 values ranging from 1.00 ± 0.01 to 271.17 ± 0.30 μM when compared to the standard drug acarbose (IC50 = 754.1 ± 0.5 μM). The kinetic binding study indicated that the most active derivatives 9b (IC50 = 1.50 ± 0.01 μM) and 9e (IC50 = 1.00 ± 0.01 μM) behaved as the uncompetitive inhibitors of α-glucosidase with Ki = 0.43 and 0.24 μM, respectively. Moreover, fluorescence measurements were conducted to show conformational changes of the enzyme after binding of the most potent inhibitor (9e). Calculation of standard enthalpy (ΔHm°) and entropy (ΔSm°) values confirmed the construction of hydrophobic interactions between 9e and the enzyme. Also, docking studies indicated desired interactions with important residues of the enzyme which rationalized the in vitro results.

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“…Recently, the literature has witnessed the identification of a plethora of promising α‐glucosidase inhibitors with novel and diverse chemistry (Ghani, 2020). Some of these include benzimidazole‐based hydrazones (Ahmad et al., 2021), usnic acid derivatives (Nguyen et al., 2021), tri‐amide derivatives (Mohammadi et al., 2021), indole‐based thiadiazole derivatives (Alomari et al., 2021) and novel ursolic acid analogs (Wu et al., 2017). Additionally, a number of dithiocarbamate derivatives conjugated with coumarin moiety have also been studied that exhibit potent inhibition of α‐glucosidase.…”

Section: Introductionmentioning

confidence: 99%

Dithiocarbamate derivatives inhibit α‐glucosidase through an apparent allosteric site on the enzyme

et al. 2021

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Synthesis of indole-based-thiadiazole derivatives as a potent inhibitor of α-glucosidase enzyme along with in silico study

Cited by 38 publications

References 47 publications

Synthesis of 1,2,3-benzotriazin-4(3H)-one derivatives as α-glucosidase inhibitor and their in-silico study

Synthesis of 1,2,3-benzotriazin-4(3H)-one derivatives as α-glucosidase inhibitor and their in-silico study

Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors

Dithiocarbamate derivatives inhibit α‐glucosidase through an apparent allosteric site on the enzyme

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