Progress on G-quadruplex as targets in anticancer drug structure screening and rational designc

Based on the recognition of bio-target molecules, screening novel anti-cancer drugs has become one of the research focuses. The revealing of the relationship between the G-quadruplex and cancer by modern molecular biology techniques provides a new opportunity to the anti-cancer drugs research. A general consensus is that organic molecules that induce or stabilize G-quadruplex structures could pave the way for the discovery of novel anti-cancer agents. Therefore, it attracts the interest of chemists and biologists in the research on anticancer drug structure screening and rational design target in G-quadruplex. The present article aims to highlight recent advances in the screening and design of G-quadruplex ligands and development of the anticancer drugs. Firstly, two screening ap-proaches based on the recognition of G-quadruplex are introduced, one is fast screening of G-quadruplex ligands from natural plant extracts based on NMR, the other is screening anticancer compounds by molecular docking techniques. Secondly, the numerous ligands can be classified into four different categories on the basis of their cationic nature, (1) in situ protonation of an amine ap-pendage, (2) N-methylation of an aza-aromatic moiety, (3) the presence of a metal centre, and (4) noncationic ligands. Finally, two quadruplex-related drug candidates CX3543 and AS1411 have en-tered phase I clinical trial, and the mechanism of them has been explored.