Synthesis, Crystal Structures and Molecular Modeling of 13-Methoxy Derivatives of Sesquiterpene Lactones Ludartin and Arglabin

Data on the synthesis of new derivatives of 13-methoxy sesquiterpene lactone from the guiana series, including ludartin and arglabin, are presented. The structures of the synthesized compounds were studied using infrared (IR), ultraviolet (UV), and nuclear magnetic resonance (NMR) spectroscopy (1H and 13C). Chemical shifts, multiplicities, and integral signal intensities in the one-dimensional 1H and 13C NMR spectra were determined. The spatial structure of the new derivatives was determined using X-ray crystallographic analysis. Molecular docking of the obtained compounds with 5-lipoxygenase (PDB ID 6BP2) was performed. It was found that they could theoretically inhibit one of the enzymes of the proinflammatory cascade, 5-lipoxygenase (5-LOX). The molecule of 13-methoxyludartin (2) can participate in the formation of hydrogen bonds with amino acids of the substrate-binding cavity, as well as interact with amino acids of the alpha-helix stabilizing 5-LOX catalytic iron ion. These interactions lead to high stability of the 5-LOX-13-methoxyludartin complex in the first 70 ns of the molecular dynamics simulation.