In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor

• A small-molecule benzofuran derivative (S6) potently bound recombinantly expressed Aurora B and inhibited its activity.
• S6 showed extensive cytotoxicity against a panel of cancer cell lines.
• S6 blocked the proliferation and colony formation of cancer cells through the inhibition of endogenous Aurora activity.
• S6 suppressed the growth of liver cancer xenograft tumors and caused Aurora B inhibition in vivo.

Aurora B is a serine/threonine kinase that has a key role in mitosis and is overexpressed in cancer cells. Aberrations in Aurora B are highly correlated with tumorigenesis and cancer development, so many studies have focused on the development of Aurora B kinase inhibitors. Based on one of our previous high-throughput screening studies, we identified lead compound S6, a small-molecule benzofuran derivative that binds Aurora B and inhibits its kinase activity in vitro. S6 also displayed high selectivity for Aurora B inhibition. The cytotoxicity of S6 was assessed against a panel of 21 cancer cell lines. The cervical cancer cell line HeLa, liver cancer cell line HepG2 and colon cancer cell line SW620 were the most sensitive to S6 treatment. We found that S6 decreased the proliferation and colony formation of these three cell lines and elevated their percentages of cells in the G2/M phase of the cell cycle. S6 also inhibited phospho-histone H3 on Ser 10, a natural biomarker of endogenous Aurora B activity. The growth suppression of liver cancer QGY-7401 xenograft tumors was observed in nude mice after S6 administration, and this effect was accompanied by the in vivo inhibition of phospho-histone H3 (Ser 10). Taken together, we conclude that targeting Aurora B with compound S6 may be a novel strategy for cancer treatment, and additional studies are warranted.

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