POSPÍŠILOVÁ, J., HEGER, T., KURKA, O., KVASNICOVÁ, Marie, CHLÁDKOVÁ, A., NĚMEC, I., RÁROVÁ, Lucie, CANKAŘ, P. Atropisomeric 1-phenylbenzimidazoles affecting microtubule organization: influence of axial chirality. Organic & Biomolecular Chemistry. 2024, 22(34), 6966-6980. ISSN 1477-0520. E-ISSN 1477-0539

Benzimidazoles are frequently used in medicinal chemistry. Their anticancer effect is among the most prominent biological activities exhibited by this scaffold. Although numerous benzimidazole derivatives have been synthesized, possible atropisomerism of ortho-substituted 1-phenylbenzimidazoles has been largely overlooked. The aim of this research was to synthesize a small library of novel atropisomeric benzimidazole derivatives and explore their biological activity in various cancer and normal human cell lines. The new unique structural motif provides an interesting 3D architecture with axial chirality, which further contributes to molecular complexity and specificity. Racemates and their separated atropisomers arrested the cell cycle, caused apoptosis, and affected microtubule organization in cancer cells in vitro at different intensities. Moreover, this phenomenon was also verified by the inhibition of endothelial cell migration. These results showed that (+)-atropisomers, especially 5n, exhibit a stronger effect and show promise as agents for cancer therapy.