Discovery of novel G-quadruplex stabilizing compounds from medicinal plant & Evaluates their cellular toxicity

Abstract G-Quadruplexes (G4Q) are higher-order, four-stranded structures that can be formed by repeated guanine tracts in human genomes. In this study, we used a structure-based virtual screening of phytomolecules derived from medicinal plants in order to discover new natural DNA G4Q binders. The top 40 ligands were sorted out based on binding affinity values after completing a docking study on 314 phytomolecule samples with parallel and mixed hybrid structure. Further Thermal melting, circular dichroism, and fluorescence displacement experiment was used as a preliminary screening tool to determine the potential stabilizing properties of β-sitosterol-β-D-glucoside, and Glabrolide. The cytotoxicity experiments were conducted on HEK293T cells and found that both of the tested phyto molecules are non-toxic for up to 150 μM concentration. Based on their cytotoxic experiments at the suggested high concentration, these phyto molecules may potentially be employed as G-Quadruplex targets in future research or applications. These results suggest that the plant may be a “lead” in the future for the development of novel therapies for diseases.