Metal-free synthesis of N-fused quinazolino-quinazoline-diones as a RNA triple helix intercalator.

The development of chemical scaffolds that target highly conserved RNA received attention due to its significance in splicing, nuclear organization, and gene expression in disease progression pathways. Here, we synthesized a series of N-fused quinazolino-quinazoline-diones a PIDA-induced C-N coupling methodology to target . Interestingly, compound 2z binds to the UUG pocket of a RNA triple-helix through intercalation, evidenced from molecular docking studies, fluorescence-based assay and CD experiments. 2z exhibited cytotoxicity towards overexpressing cancer cells (SKOV-3, IC of 8.0 ± 0.4 μM). These findings demonstrated 2z as a RNA triple-helix intercalator with therapeutic potential, offering an important chemical scaffold to understand activity in disease development pathways.