Computationally-Assisted Discovery and computational NMR Assignment of a Highly-binding PXR Natural Diterpenoids

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery of a new class of 4,5-seco-abietane diterpenoids that possess anti-inflammatory bioactivity targeting the pregnane X receptor (PXR). Rubescens A represents the first in a new class of 4,5-seco-abietane diterpenoids, discovered from Isodon. rubescens (I. rubescens). The molecule was discovered with the guidance of molecular ion networking (MoIN) analysis and untargeted pull down experiment. The structure was elucidated and determined using extensive spectroscopic analysis in conjunction with computationally assisted quantifiable structure elucidation tools. In the docking study, Rubescens A binds well to PXR, COX-2 and ATP binding domain of some protein kinases involved in inflammatory pathways.