Probing the binding and interaction of curcumin-tryptophan conjugate to G-quadruplex motif via spectroscopic and molecular docking approach

Abstract

A potential ligand with the ability to interact with the structure of G-quadruplexes has been promising strategy for develop anticancer drug. Curcumin, a natural antioxidant is known to induce apoptosis in the tumour cells and was previously found as G-quadruplex binder. We investigated how the conjugation of tryptophan with curcumin affects its ability as G-quadruplex DNA binder. We have reported the differential interaction of Curcumin-tryptophan (CT) with a parallel G-quadruplex(GQ) formed by the nuclease hypersensitivity element (NHEIII) Pu27 present of the protooncogene and human telomeric G-quadruplex sequence. Taken into account, ligand CT has a stronger binding affinity for the G-quadruplex over the canonical duplex DNA. We have used biophysical approach such as uv-visible, fluorescence, circular dichroism, differential scanning calorimetry and molecular docking experiment to show that curcumin tryptophan interacts with the G-quadruplex. The results indicate that CT has a binding affinity of 106 M−1 for G-quadruplexes. Thermodynamic studies show that the ligand CT destabilizes the G-quadruplexes (6–8 °C) due to aromatic core stacking between the tetrad. The anti-proliferative experiment of the synthesized ligand CT in vitro on several cancer cell lines such as HeLa cells and MCF-7 cell lines shows that it is more effective against MCF-7. Thus, present studies report Curcumin-tryptophan as a potential G-quadruplex binder that destabilizes the quadruplex structure .