Design, Synthesis, and Molecular Docking of a Novel Pyrimidine Terminal Alkyne Antitumor Agent

Five compounds were successfully synthesized through several simple steps. Alkynyl plays an indispensable role in the structural modification of drugs. In this paper, alkynyl and benzene rings were introduced into the mother nucleus of pyrimidine derivatives to obtain single and double alkynyl compounds. The five compounds have similar photophysical properties. The cytotoxicity test in vitro was carried out by MTT assay. The results showed that the activity of single alkynyl compounds were better than that of double alkynyl compounds. In order to simulate the binding between the compound and the target protein, molecular docking was carried out by Molecular operating environment (MOE) software package version AutoDock Vina 1.1.2. Four proteins (JNK3, Bcr-Abl kinase, MAP3K, and Topo II) were selected for simulation. The results showed that hydrogen-bonding, π-π bond and hydrophobic interaction were the main forces. In addition, it is interesting that after structural modification, the compound has a higher affinity for docking with the protein than the starting material, and the compound was better captured by the protein. This lays a foundation for the research and development of new drugs and has a certain reference value in the research of antitumor agents.