Selective Recognition of <i>c-KIT 1</i> G-Quadruplex by Structural Tuning of Heteroaromatic Scaffolds and Side Chains

Abstract

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