Enhanced biophysical, electrochemical and computational recognition of cancer-relevant G-quadruplex DNA by ferrocenyl curcumin Schiff base motifs

Abstract

G-quadruplex DNA structures located in promoter and telomeric regions play critical roles in gene regulation and cancer progression, making them attractive targets for small-molecule intervention. In this study, we report the design and synthesis of a novel ferrocenyl curcumin-based Schiff base ligand (Sb-Fc) and systematically investigate its interaction with G-quadruplex DNA, namely the c-MYC promoter (Pu27) and human telomeric (H-telo) sequences. Spectroscopic studies reveal a strong binding preference of Sb-Fc for G-quadruplex DNA over duplex DNA. Electrochemical investigations show that Sb-Fc-modified gold electrodes exhibit enhanced redox reversibility and enable sensitive detection of G-quadruplex DNA, with detection limits of 6.74 ± 0.2 nM for Pu27 and 8.41 ± 0.5 nM for H-telo. Complementary density functional theory and molecular docking studies corroborate the experimental findings, revealing favourable electronic properties and preferential binding of Sb-Fc to parallel G-quadruplex DNA via electrostatic and stacking interactions. Collectively, these results establish Sb-Fc as a versatile redox-active scaffold for G-quadruplex targeting and biosensing applications.