Syntheses and Evaluation of New Bisacridine Derivatives for Dual Binding of G-Quadruplex and i-Motif in Regulating Oncogene Expression.

The oncogene is an important regulator for cell growth and differentiation, and its aberrant overexpression is closely related to the occurrence and development of various cancers. Thus, the suppression of transcription and expression has been investigated for cancer treatment. In this study, various new bisacridine derivatives were synthesized and evaluated for their binding with promoter G-quadruplex and i-motif. We found that could bind to and stabilize both G-quadruplex and i-motif, resulting in the downregulation of gene transcription. could inhibit cancer cell proliferation and induce SiHa cell apoptosis and cycle arrest. exhibited tumor growth inhibition activity in a SiHa xenograft tumor model, which might be related to its binding with promoter G-quadruplex and i-motif. Our results suggested that as a dual G-quadruplex/i-motif binder could be effective in both oncogene replication and transcription and become a promising lead compound for further development with improved potency and selectivity.