Synthesis, butyrylcholinesterase inhibitory activity and molecular docking of novel hydroxylated 2-benzylbenzofuran derivatives

A benzofuran ring as a core of heterocyclic compounds is an essential structural unit of various biologically active natural medicines and synthetic chemical raw materials. Numerous studies have shown that 2-phenylbenzofurans have strong biological activities such as anti-cancer, anti-bacterial, anti-viral, anti-oxidative, anti-fungal and anti-microbial. Recent studies have demonstrated enzymatic inhibition properties of 2-phenylbenzofuran derivatives, for example, against butyrylcholinesterase and monoamine oxidase.

In our efforts to contribute to the development of novel compounds that may be useful in the treatment of neurodegenerative disorders such as Parkinson’s disease or Alzheimer’s disease, we are focusing on benzofuran substituted at the position 2 from a benzyl ring.

A preliminary study gives some insights into the synthesis and biological activity of these molecules against this important target. The position of hydroxyl group on the 2-benzyl ring and the position of halogen atom in the benzofuran nucleus, have an important influence on the inhibitory activity. The observed structure-activity relationship for these compounds was explain by molecular docking.

Further studies are still needed to optimize the structure and interaction with the enzyme, with the aim of increasing the potential of these molecules as inhibitors.