Femtomolar inhibition by a virtually designed molecule: Pseudoeriocitrin as a potent inhibitor

Pseudoeriocitrin is a virtually designed molecule created in silico by assuming the formation of oxygen radicals in eriocitrin, resulting in a different geometry. It achieves femtomolar-level inhibition in in silico docking studies, demonstrating higher inhibitory efficacy than eriocitrin. This study investigated the mechanisms underlying the extraordinary inhibitory activity of pseudoeriocitrin through a 3D analysis of potential interactions using an in silico protein-ligand docking method. Although it is difficult to reach a definitive conclusion, the absence of hydrogen donors renders the pseudoeriocitrin structure highly toxic. The high binding affinity of pseudoeriocitrin, which inhibits various proteins at the femtomolar level, with the lowest inhibition constant value of 3.45 fM, is presumably due to its planar structure and the abundance of oxygen radicals, which facilitate the formation of hydrogen bonds with atoms in the active site of the proteins. This study is the first to demonstrate the structure-activity relationship of pseudoeriocitrin through in silico docking method. The results indicate that the large core structure, abundance of oxygen atoms, planar geometry, and femtomolar-level inhibition are interrelated. The chemical properties resulting from these unique biological properties should be examined from multiple perspectives. In addition, further research is required to explore the synthesis of non-radical pseudoeriocitrin.