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6-氯-2-芳基-1H-咪唑并[4,5-b]吡啶衍生物的合成:抗糖尿病、抗氧化、β-葡萄糖醛酸酶抑制作用及其分子对接研究。

Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic, antioxidant, β-glucuronidase inhibiton and their molecular docking studies.

作者信息

Taha Muhammad, Ismail Nor Hadiani, Imran Syahrul, Rashwan Hesham, Jamil Waqas, Ali Sajjad, Kashif Syed Muhammad, Rahim Fazal, Salar Uzma, Khan Khalid Mohammed

机构信息

Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.

Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Science UiTM, 40450 Shah Alam, Selangor, Malaysia.

出版信息

Bioorg Chem. 2016 Apr;65:48-56. doi: 10.1016/j.bioorg.2016.01.007. Epub 2016 Feb 1.

Abstract

6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50μM) and 4 (IC50=240.30±2.90μM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50μM), 6 (IC50=290.60±3.60μM), 13 (IC50=288.20±3.00μM) and 26 (IC50=292.10±3.20μM) also showed better activities than the standard rutin (IC50=294.50±1.50μM). In antioxidant assay, compound 1 (IC50=69.45±0.25μM), 2 (IC50=58.10±2.50μM), 3 (IC50=74.25±1.10μM), and 4 (IC50=72.50±3.30μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC50=29.25±0.50μM), compound 1 (IC50=30.10±0.60μM) and compound 4 (IC50=46.10±1.10μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25μM) and their interaction with the enzyme was confirm by docking studies.

摘要

合成了6-氯-2-芳基-1H-咪唑并[4,5-b]吡啶衍生物1-26,并通过各种光谱技术对其进行了表征。对所有这些衍生物进行了抗糖化、抗氧化和β-葡萄糖醛酸酶活性评估,并随后进行了对接研究。在抗糖化试验中,发现化合物2(IC50=240.10±2.50μM)和4(IC50=240.30±2.90μM)是该系列中活性最高的化合物,而化合物3(IC50=260.10±2.50μM)、6(IC50=290.60±3.60μM)、13(IC50=288.20±3.00μM)和26(IC50=292.10±3.20μM)的活性也优于标准芦丁(IC50=294.50±1.50μM)。在抗氧化试验中,化合物1(IC50=69.45±0.25μM)、2(IC50=58.10±2.50μM)、3(IC50=74.25±1.10μM)和4(IC50=72.50±3.30μM)表现出良好的活性。在β-葡萄糖醛酸酶活性方面,与标准D-糖二酸1,4-内酯(IC50=48.50±1.25μM)相比,化合物3(IC50=29.25±0.50μM)、化合物1(IC50=30.10±0.60μM)和化合物4(IC50=46.10±1.10μM)表现出显著活性,并且通过对接研究证实了它们与该酶的相互作用。

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