Background: Guanine-rich DNA regions can fold into G-quadruplex (G4) structures, which are prevalent in telomeres and oncogene promoters, making them attractive targets for anticancer therapeutics. Small molecules capable of selectively stabilizing G4 DNA can disrupt telomerase activity and oncogene expression, offering a promising strategy for cancer intervention. Methods: A rationally designed series of DPPZ-anhydride-conjugated ligands (1 and 2) and their corresponding quaternized derivatives (1-q and 2-q) were synthesized to investigate the combined effects of pi-extension, bromine substitution, and cationic modification on DNA recognition. The synthetic strategy relied on the incorporation of a highly planar DPPZ-anhydride scaffold to enhance pi-surface area, followed by selective quaternization to introduce permanent positive charge and reinforce electrostatic interactions with the DNA backbone. All compounds were fully characterized by NMR and spectroscopic methods. The DNA-binding properties of the ligands were systematically evaluated toward duplex (ds-DNA) and G-quadruplex (G4-DNA) structures using UV-Vis absorption titration, fluorescence intercalator displacement (FID) assays, and competitive dialysis experiments. Quaternization markedly enhanced intrinsic binding constants and significantly reduced DC50 values, particularly for G4-DNA. While bromine substitution increased overall binding affinity, it did not substantially improve topology selectivity. Among the series, compound 1-q exhibited the most favorable balance between affinity and G4 selectivity. Results: The interaction of the compounds with BSA was quantified using Stern-Volmer quenching constants, which demonstrated a clear trend of enhanced quenching efficiency upon modification. The binding strength followed a descending order of 1-q > 2-q > 1 > 2, highlighting the superior performance of the first series over the second. These findings indicate that the structural features of 1-q facilitate a more robust interaction within the hydrophobic pockets of the protein. Conclusions: Overall, the results demonstrate that strategic pi-conjugation combined with electrostatic reinforcement provides an effective approach for the development of topology-selective DNA-binding ligands.