Synthesis of terphenyl benzimidazoles as tubulin polymerization inhibitors

A series of new terphenyl benzimidazoles (3a–z and 3aa–ad) were synthesized and evaluated for their anticancer activity. All the 30 compounds have shown moderate to good anticancer potency, however some of the compounds (3j, 3m−t and 3aa−ad) exhibited prominent anticancer potency with GI50 values ranging from <0.1 to 9.72 μM. These compounds exhibit G2/M phase arrest and the analysis of tubulin by Western blot experiments in case of 3t and 3ad shows the disturbances that are caused in the ratio of soluble versus polymerized tubulin in cells. Compounds 3t and 3ad are the most promising candidates amongst the series and has the potential to be taken up for further detailed studies either alone or in combination with the existing therapies.

Graphical abstractA library of terphenyl benzimidazole compounds were prepared and evaluated for anticancer activity. Further, some of the biological assays were also carried.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 30 Novel terphenyl benzimidazoles were synthesized and evaluated for their anticancer potency. ► Suzuki coupling reaction has been utilized. ► G2/M phase arrest in A-549 cell lines. ► Inhibition’ of tubulin polymerization. ► Compounds 3t and 3ad could be promising anticancer agents for anticancer chemotherapy.