Computational studies of the interactions between quinazolone derivatives and G-quadruplex DNA as an anticancer strategy

Abstract

In recent years, stabilization of G-quadruplex structures with small molecules has attracted considerable attentions as a promising target for cancer therapy. Quinazolone derivatives (QD) are among the most important classes of ligands that is designed and synthesized to stabilize G-quadruplex structures. Understanding the nature of interactions between the ligands and G-quadruplex is of great importance. To precisely investigate how these interactions can be influenced by structural variation of the ligand, binding interactions of two quinazolone derivatives (QD1 and QD2) with G-quadruplex were studied by molecular docking and molecular dynamics simulation. The results revealed that ligand QD1 has stronger interactions with G-quadruplex than QD2. In fact, side chain shortening of these derivatives play a crucial role in hydrogen bond formation and electrostatic interactions with the phosphate backbone of G-quadruplex which is not obtained experimentally.

Keywords

• g-quadruplex
• quinazolone
• molecular docking
• molecular dynamics simulation
• free energy