The microtubule cytoskeleton: A validated target for the development of 2-Aryl-1H-benzo[d]imidazole derivatives as potential anticancer agents - 04/02/24
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.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Benzimidazole derivatives were designed to target the microtubule networks. |
• | Compounds O-7 and O-10 showed selectivity indexes of 151.7 and 61.9, respectively. |
• | O-7 (IC50 = 0.236) and O-10 (IC50 = 0.622) showed potent anticancer activity. |
• | O-7 impede cancer cell migration by inhibiting wound closure and colony formation. |
• | MoA of O-7 indicates G2/M cell cycle arrest followed by early appoptosis. |
Keywords : Microtubule, Cytoskeleton, Destabilizing agents, Benzimidazole, Tubulin, Polymerization, Inhibitor, Colchicine, Nocodazole
Plan
Vol 171
Article 116106- février 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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