Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia.
KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Virology and Chemotherapy, Rega Institute, 3000 Leuven, Belgium.
Molecules. 2023 Oct 21;28(20):7208. doi: 10.3390/molecules28207208.
A series of novel 2,6-diphenyl substituted imidazo[4,5-]pyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity . The conditions of the Suzuki coupling were evaluated and optimized using a model reaction. To study the influence of the substituents on the biological activity, we prepared -unsubstituted and -methyl substituted imidazo[4,5-]pyridines with different substituents at the position on the phenyl ring placed at position 6 on the heterocyclic scaffold. Antiproliferative activity was determined on diverse human cancer cell lines, and the selectivity of compounds with promising antiproliferative activity was determined on normal peripheral blood mononuclear cells (PBMC). Pronounced antiproliferative activity was observed for -hydroxy substituted derivatives and , both displaying strong activity against most of the tested cell lines (IC 1.45-4.25 μM). The unsubstituted -methyl derivative proved to be the most active derivative. There was a dose-dependent accumulation of G2/M arrested cells in several cancer cell lines after exposure to compound , implying a cell cycle-phase-specific mechanism of action. Additionally, the novel series of derivatives was evaluated for antiviral activity against a broad panel of viruses, yet the majority of tested compounds did not show antiviral activity.
设计并合成了一系列新型 2,6-二苯基取代的咪唑并[4,5-b]吡啶，采用优化的 Suzuki 交叉偶联反应来评估它们的生物活性。通过模型反应对 Suzuki 偶联条件进行了评估和优化。为了研究取代基对生物活性的影响，我们在杂环骨架的 6 位苯环上制备了不同取代基的 -未取代和 -甲基取代的咪唑并[4,5-b]吡啶。在多种人类癌细胞系上测定了抗增殖活性，并在正常外周血单核细胞 (PBMC) 上测定了具有良好抗增殖活性的化合物的选择性。-羟基取代衍生物 和 表现出显著的抗增殖活性，对大多数测试的细胞系均显示出较强的活性 (IC 1.45-4.25 μM)。未取代的 -甲基衍生物 是最具活性的衍生物。在几种癌细胞系中，化合物 暴露后会出现 G2/M 期阻滞细胞的剂量依赖性累积，这表明其作用机制具有细胞周期特异性。此外，还评估了一系列新型衍生物的抗病毒活性，然而大多数测试的化合物都没有显示出抗病毒活性。
