Abstract：
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 IC50 value of 0.236 ± 0.096 μM, while O-10 showed an IC50 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 G2/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.
摘要：
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在各种测试细胞系中显示出令人印象深刻的抗增殖活性，显示选择性指数分别为151.7和61.9。O-7的IC50值为0.236±0.096μM，而O-10对A549细胞系的IC50值为0.622±0.13μM。以剂量依赖性方式诱导早期凋亡进一步强调了O-7和O-10作为有效抗增殖剂的潜力。O-7和O-10对伤口闭合有显著抑制作用，伤口闭合百分比从0μM的23%下降到20μM的0.43%和2.62%，分别。殖民地形成的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可以阻止癌细胞迁移并具有抑制集落形成的高潜力。对O-7和O-10的作用方式研究表明，O-7可以抑制体外微管蛋白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G2/M期，表明O-7通过微管不稳定发挥其抗癌活性。然而,O-10显示了与O-7不同的作用模式，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，激发对其药理特性和治疗应用的进一步探索。
