Synthesis of hydrazine containing piperazine or benzimidazole derivatives and their potential as α-amylase inhibitors by molecular docking, inhibition kinetics and in vitro cytotoxicity activity studies

Cakmak, Ummuhan; Oz-Tuncay, Fulya; Basoglu-Ozdemir, Serap; Demir, Elif; Demir, Ilke; Çolak, Ahmėt; Çelik-Uzuner, Selcen; Erdem, Safiye Sağ; Yıldırım, Nuri

doi:10.1007/s00044-021-02785-8

Cited by 9 publications

(10 citation statements)

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“…In addition, some benzimidazole derivatives are well recognized for their antidiabetic potential, especially as potent α-glucosidase and α-amylase inhibitors. A multitude of benzimidazole derivatives were reviewed as α-amylase inhibitors including benzimidazole bearing sulfonamide [ 34 ], 2-arylbenzimidazole [ 35 ], 2-mercaptobenzimidazole [ 36 ], 2-aminobenzimidazole derivatives [ 37 ], substituted benzimidazole analogs [ 38 ], 2-(2-methyl-5-nitro-1 H -imidazol-1-yl)ethylaryl ether [ 39 ], and benzimidazole-based Cu (II)/Zn (II) complexes [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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 mass spectra were obtained at MALDI‐TOF/MS (UltrafleXtreme, Bruker). Ester ( 2 ) and hydrazide ( 3 ) compounds were prepared by previously reported procedures [47] …”

Section: Methodsmentioning

confidence: 99%

“…(2) [47] The solution of 1H-benzo[d]imidazol-2-amine (10 mmol) in tetrahydrofuran was stirred in the presence of triethylamine (30 mmol) for 15 minutes at room temperature. Ethyl bromoacetate (15 mmol) was added dropwise in an ice bath and stirred for 30 minutes.…”

Section: Synthesis Of Ethyl (1h-benzo[d]imidazol-2-yl)glycinatementioning

confidence: 99%

Synthesis, Biological Investigation, and Molecular Docking of Novel Benzimidazole‐Hydrazone Hybrids as Potential Anticancer Agent Candidates

Demirci,

Köprülü,

Mermer

et al. 2024

ChemistrySelect

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In this study, six novel Benzimidazole‐hydrazone derivatives starting from the commercially available 1H‐benzo[d]imidazole‐2‐amine were synthesized, and the molecular structure of the obtained compounds were confirmed by NMR, FTIR and MS spectroscopic techniques. The anticancer activities of the synthesized compounds were investigated against HT29 (Human colon adenocarcinoma) and A549 (Human non‐small cell lung cancer) cancer cell lines using xCELLigence real‐time cell analysis. Cell apoptosis was determined by DNA laddering assay and Annexin V/FITC flow cytometer. Compound 4 c exhibited the best anticancer potency against both cancer cell lines (A549 and HT29) with IC50 values of 0.0019 μM and 0.0093 μM, respectively. Compound 4 c reduced the growth of A549 and HT29 cells in vitro and induced early apoptosis of A549 and HT29 cells. Additionaly, all compounds demonstrated favorable pharmacokinetics properties compared to Paclitaxel (reference compound) and the best docking scores were obtained for compounds 4 e and 4 b among the compounds.

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“…The results of percentage absorption (% ABS), topological polar surface area (TPSA), number of rotatable bonds (n-ROTB), molecular volume (MV), molecular weight (MW), the logarithm of partition coefficient of compound between n-octanol and water (miLog P), number of hydrogen bond acceptors (n-ON acceptors), number of hydrogen bonds donors (n-OHNH donors) of the compounds and kojic acid are shown in Table 1. Eighteen compounds (excluding only the molecular weight characteristic of compounds 7a-b, 9a-9b) were found to meet Lipinski's Five Rules (MW ≤ 500 g/mol; LogP ≤ 5 (or MLogP ≤ 4.15); n-OHNH donors ≤ 5, n-ON acceptors ≤ 10 and (TPSA) Å² < 140 Å²) [20,21]. In addition, the % ABS values of the compounds vary between 67.3% and 75.7%.…”

Section: Determination Of Adme Propertiesmentioning

confidence: 99%

Antityrosinase Activities and in silico ADME Properties of Fluorine-containing 1,2,4-triazole-5-on Derivatives

Cakmak

Tuncay

2022

Hacettepe Journal of Biology and Chemistry

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Bu çalışmada, flor içeren 1,2,4-triazol-5-on türevlerinin (2a-b, 3a-b, 4a-d, 5a-b, 6a-b, 7a-b, 8a-b ve 9a-b) klinik öneme sahip tirosinaz enziminin aktivitesi üzerine inhibisyon potansiyelleri incelenmiştir. Moleküllerin IC50 değerleri belirlenmiştir. Moleküller arasında en iyi inhibisyon özelliği gösteren molekülün inhibisyon türü ve Ki değeri hesaplanmıştır. Ticari olarak temin edilen mantar tirosinaz için optimum reaksiyon şartları belirlendikten sonra, kinetik çalışmalar yapılarak en düşük IC50 değerine sahip molekülün 8b olduğu tespit edilmiştir. Referans inhibitör molekül olarak kullanılan kojik aside (IC50=45,7±0,9 µM) göre 8a-b, 9a-b (IC50 değerleri sırasıyla 32,2±0,7 µM; 22,9±0,6 µM; 22,8±0,5 µM; 23,8±0,6 µM) moleküllerinin tirosinaz aktivitesi üzerinde oldukça etkili inbitör özelliğine sahip olduğu tespit edilmiştir. 8b molekülü için inhibisyon türü nonkompetetif olarak belirlenmiş ve Ki değeri 6,09±0,12 µM olarak hesaplanmıştır. Ayrıca tüm moleküllerin ADME özellikleri de incelenmiş olup, her bir molekülün ilaç aday molekülü olarak yüksek bir potansiyele sahip olduğu tespit edilmiştir. Bu sonuçlar neticesinde 8a-b ve 9a-b molekülleri, tirosinaz aktivitesine karşı oldukça etkili ve umut verici inhibitör bileşikler olarak kabul edilebilir.

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Synthesis of hydrazine containing piperazine or benzimidazole derivatives and their potential as α-amylase inhibitors by molecular docking, inhibition kinetics and in vitro cytotoxicity activity studies

Cited by 9 publications

References 61 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

Synthesis, Biological Investigation, and Molecular Docking of Novel Benzimidazole‐Hydrazone Hybrids as Potential Anticancer Agent Candidates

Antityrosinase Activities and in silico ADME Properties of Fluorine-containing 1,2,4-triazole-5-on Derivatives

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