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

ABSTRACT: 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 mec

SUBMITTER: Fatma K 

PROVIDER: S-EPMC10945540 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature