Development and Characterization of Benzoselenazole Derivatives as Potent and Selective Transcription Inhibitors.

Developing transcription inhibitors that target the G-quadruplex has generated significant interest; however, few compounds have demonstrated specificity for G-quadruplex and cancer cells. In this study, we designed and synthesized a series of benzoazole derivatives as potential G-quadruplex ligand-based transcription inhibitors. Surprisingly, benzoselenazole derivatives, which are rarely reported as G-quadruplex ligands, demonstrated greater G-quadruplex selectivity and cancer cell specificity compared to their benzothiazole and benzoxazole analogues. The most promising compound, benzoselenazole , selectively inhibited transcription by specifically stabilizing the G-quadruplex. This led to selective inhibition of hepatoma cell growth and proliferation by affecting the MYC target gene network, as well as effective tumor growth inhibition in hepatoma xenografts. Collectively, our study demonstrates that holds significant promise as a potent and selective inhibitor of transcription for cancer treatment. Furthermore, our findings inspire the development of novel selenium-containing heterocyclic compounds as G-quadruplex-specific ligands and transcription inhibitors.