Development of axially chiral urazole scaffolds for antiplant virus applications against potato virus Y

Abstract

BACKGROUND: Potato virus Y (PVY) was first discovered by Smith in 1931 and is currently ranked as the fifth most significant plant virus. It can cause severe damage to plants from the family Solanaceae, which results in billions of dollars of economic loss worldwide every year. To discover new antiviral drugs, a class of multifunctional urazole derivatives bearing a stereogenic C-N axis were synthesized with excellent optical purities for antiviral evaluations against PVY. RESULTS: The absolute configurations of the axially chiral compounds exhibited obvious distinctions in antiviral bioactivities, with several of these enantio-enriched axially chiral molecules showing excellent anti-PVY activities. In particular, compound (R)-9f exhibited remarkable curative activities against PVY with a 50% maximal effective concentration (EC50) of 224.9 μg mL−1, which was better than that of ningnanmycin (NNM), which had an EC50 of 234.0 μg mL−1. And the EC50 value of the protective activities of compound (R)-9f was 462.2 μg mL−1, which was comparable to that of NNM (442.0 μg mL−1). The mechanisms of two enantiomer of the axially chiral compounds 9f were studied by both molecule docking and defensive enzyme activity tests. CONCLUSION: Mechanistic studies demonstrated that the axially chiral configurations of the compounds played significant roles in the molecule PVY-CP (PVY Coat Protein) interactions and could enhance the activities of the defense enzymes. The (S)-9f showed only one carbon–hydrogen bond and one π–cation interaction between the chiral molecule and the PVY-CP amino acid sites. In contrast, the (R)-enantiomer of 9f exhibited three hydrogen bonding interactions between the carbonyl groups and the PVY-CP active sites of ARG157 and GLN158. The current study provides significant information on the roles that axial chiralities play in plant protection against viruses, which will facilitate the development of novel green pesticides bearing axial chiralities with excellent optical purities.