Design, Synthesis, and Biophysical Characterization of Pyridine Bis-Quinazoline Derivatives as Selective G-Quadruplex DNA Stabilizers.

ABSTRACT: Non-canonical G-quadruplex (G4) DNA structures play key roles in cellular regulation and are promising targets for cancer therapy. This study reports the design, synthesis, and biophysical evaluation of 15 novel pyridine bis-quinazoline derivatives for their ability to selectively bind and stabilize G4 DNA structures. The pyridine-bis-quinazoline central fragment was synthesized with various amine side chains via a 4-5 step sequence in high yields. Comprehensive analyses using different fluorescence resonance energy transfer (FRET) assays, fluorescence intercalator displacement (FID), circular dichroism (CD), and nuclear magnetic resonance (NMR) assays revealed strong G4 stabilization and selectivity over double-stranded DNA. The presence and composition of the aliphatic amine side chain p

SUBMITTER: Nath Das R 

PROVIDER: S-EPMC11979681 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature