Selective Recognition of c-KIT 1 G-Quadruplex by Structural Tuning of Heteroaromatic Scaffolds and Side Chains.

In this study, carbazole ( MC ) and dibenzofuran ( MD ) derivatives were synthesized to examine their effect on the biomolecular recognition of G-quadruplex (G4) targets. Biophysical studies revealed that MC-4 , a carbazole derivative, exhibits a specific affinity and effectively stabilizes the c-KIT 1 G4. Molecular modeling suggests a stable interaction of MC-4 with the terminal G-tetrad of c-KIT 1 G4. Biological studies demonstrate that MC-4 efficiently enters cells, reduces c-KIT gene expression, and induces cell cycle arrest, DNA damage, and apoptosis in cancer cells. These findings demonstrate MC-4 as a selective c-KIT G4 ligand with therapeutic potential, providing insight into the structural basis of its anticancer mechanisms.