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

Document Type : Original Article



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.