Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200702, South Korea.
Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 200702, South Korea.
Biomed Pharmacother. 2024 Feb;171:116106. doi: 10.1016/j.biopha.2023.116106. Epub 2024 Jan 4.
In this study, a series of 2-Aryl-1H-benzo[d]imidazole derivatives were developed to target intra- and extracellular microtubule networks. Compounds O-7 and O-10 showed impressive anti-proliferative activity across various tested cell lines, demonstrating selectivity indexes of 151.7 and 61.9, respectively. O-7 achieved an IC value of 0.236 ± 0.096 μM, while O-10 showed an IC value of 0.622 ± 0.13 μM against A549 cell lines. The induction of early-stage apoptosis in a dose-dependent manner further underscored the potential of O-7 and O-10 as effective anti-proliferative agents. O-7 and O-10 exhibited substantial inhibition of wound closure, with wound closure percentages decreasing from 23% at 0 μM to 0.43% and 2.62% at 20 μM, respectively. Colony formation reduction rates were impressive, with O-7 at 74.2% and O-10 at 81.2%. These results indicate that the O-7 and O-10 can impede cancer cell migration and have a high potential to curtail colony formation. The mode of action investigations for O-7 and O-10 revealed that O-7 could inhibit in vitro tubulin polymerization and disrupt the intracellular microtubule cytoskeleton. This disruption led to cell cycle arrest in the G/M phase, indicating that O-7 exerts its anticancer activity through microtubule destabilization. However, O-10 shows a different mode of action than O-7 and requires further investigation. Overall, our study showcases the potential of the synthesized benzimidazole derivatives as novel and selective anticancer agents, motivating further exploration of their pharmacological properties and therapeutic applications.
在这项研究中，开发了一系列 2-芳基-1H-苯并[d]咪唑衍生物，以靶向细胞内和细胞外微管网络。化合物 O-7 和 O-10 在各种测试的细胞系中表现出令人印象深刻的抗增殖活性，其选择性指数分别为 151.7 和 61.9。O-7 的 IC 值为 0.236±0.096 μM，而 O-10 对 A549 细胞系的 IC 值为 0.622±0.13 μM。以剂量依赖方式诱导早期细胞凋亡进一步强调了 O-7 和 O-10 作为有效抗增殖剂的潜力。O-7 和 O-10 对伤口闭合有显著的抑制作用，从 0 μM 的 23%到 20 μM 的 0.43%和 2.62%，分别减少了伤口闭合百分比。集落形成减少率令人印象深刻，O-7 为 74.2%，O-10 为 81.2%。这些结果表明，O-7 和 O-10 可以阻碍癌细胞迁移，并具有抑制集落形成的高潜力。对 O-7 和 O-10 的作用机制研究表明，O-7 可以抑制体外微管聚合并破坏细胞内微管细胞骨架。这种破坏导致细胞周期停滞在 G/M 期，表明 O-7 通过微管不稳定发挥其抗癌活性。然而，O-10 与 O-7 的作用模式不同，需要进一步研究。总的来说，我们的研究展示了合成的苯并咪唑衍生物作为新型和选择性抗癌剂的潜力，激励进一步探索它们的药理学特性和治疗应用。
