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Gene expression and tumor growth can be regulated by methylation levels of lysine residues on histones, which are controlled by histone lysine demethylases (KDMs). Series of benzo[ b ]tellurophene and benzo[ b ]selenophene compounds were designed and synthesized and they were evaluated for histone H3 lysine 9 demethylase (KDM4) inhibitory activity. Among the carbamates, alcohol and aromatic derivatives, tert-butyl benzo[ b ]tellurophen-2-ylmethylcarbamate (compound 1c) revealed KDM4 specific inhibitory activity in cervical cancer HeLa cells, whereas the corresponding selenium or oxygen substitute compounds did not display any inhibitory activity toward KDM4. Compound 1c also induced cell death in cervical and colon cancer but not in normal cells. Thus, compound 1c, a novel inhibitor of KDM4, constitutes a potential therapeutic and research tool against cancer.

Benzo[b]tellurophenes as a Potential Histone H3 Lysine 9 Demethylase (KDM4) Inhibitor