Axial Chirality and Antiviral Activity Evaluation of Arylnaphthalene Lignan Glycosides from Justicia procumbens

Abstract

One of the structural uniqueness of arylnaphthalene lignans (ANLs) is their potential atropoisomerism, which may result in bioactivity discrepancy. However, the stable ANL atropisomers rarely exist in nature. In the course of our phytochemical study of Justicia procumbens, we isolated nine ANL glycosides (1-9) with four of them (1-4) being identified as new stable atropisomers. Their absolute configurations were determined based on the analysis of the circular dichroism (CD) and electronic circular dichroism (ECD) data.The ANL compounds were evaluated for their antiviral potential as entry inhibitors against the infections of H5N1 influenza virus, vesicular stomatitis virus (VSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with 5 being the most potent one with IC 50 values ranging from 0.0063-1.13 μM. The atropisomers did not display significant antiviral activity, indicating that a free rotation of the biphenyl aryl-aryl bond could play a significant role in the antiviral activity of ANL compounds.