新型取代苯并咪唑衍生酰胺的设计、合成、生物评价及 QSAR 分析。

Design, synthesis, biological evaluation and QSAR analysis of novel -substituted benzimidazole derived carboxamides.

机构信息

Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Zagreb, Croatia.

Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.

出版信息

J Enzyme Inhib Med Chem. 2022 Dec;37(1):1327-1339. doi: 10.1080/14756366.2022.2070910.

As a result of our previous research focussed on benzimidazoles, herein we present design, synthesis, QSAR analysis and biological activity of novel N-substituted benzimidazole derived carboxamides. Carboxamides were designed to study the influence of the number of methoxy groups, the type of the substituent placed at the benzimidazole core on biological activity. Pronounced antioxidative activity displayed unsubstituted (IC ≈ 3.78 mM, 538.81 mmolFe/mmolC) and dimethoxy substituted derivative (IC ≈ 5.68 mM, 618.10 mmolFe/mmolC). Trimethoxy substituted and unsubstituted compound with isobutyl side chain at N atom showed strong activity against HCT116 (IC ≈ 0.6 µM, both) and H 460 cells (IC ≈ 2.5 µM; 0.4 µM), being less cytotoxic towards non-tumour cell. Antioxidative activity in cell generally confirmed relatively modest antioxidant capacity obtained in DPPH/FRAP assays of derivatives and . The 3D-QSAR models were generated to explore molecular properties that have the highest influence on antioxidative activity.

基于我们之前对苯并咪唑的研究，本文设计、合成了一系列新型 N-取代苯并咪唑甲酰胺衍生物，并对其进行了定量构效关系（QSAR）分析和生物活性研究。我们设计了这些甲酰胺衍生物，旨在研究苯并咪唑核心上取代基的数量和类型对生物活性的影响。结果显示，未取代的苯并咪唑甲酰胺（IC≈3.78mM，538.81mmolFe/mmolC）和二甲氧基取代的衍生物（IC≈5.68mM，618.10mmolFe/mmolC）具有显著的抗氧化活性。而三氧基取代的苯并咪唑甲酰胺衍生物和带有异丁基侧链的未取代化合物在 N 原子上表现出对 HCT116（IC≈0.6µM，两者）和 H 460 细胞（IC≈2.5µM；0.4µM）的强烈抑制作用，对非肿瘤细胞的细胞毒性较低。细胞抗氧化活性一般证实了衍生物和的 DPPH/FRAP 测定中获得的相对适中的抗氧化能力。我们还生成了 3D-QSAR 模型，以探索对抗氧化活性影响最大的分子性质。