Generation of potent antibacterial compounds through enzymatic and chemical modifications of the trans-δ-viniferin scaffold
Robin Huber, Laurence Marcourt, Margaux Héritier, Alexandre Lüscher, Laurie Guebey, Sylvain Schnée, Emilie Michellod, Stéphane Guerrier, Jean‐Luc Wolfender, Léonardo Scapozza, Thilo Köhler, Katia Gindro, Emerson Ferreira Queiroz
Abstract
Stilbene dimers are well-known for their diverse biological activities. In particular, previous studies have demonstrated the high antibacterial potential of a series of trans-δ-viniferin-related compounds against gram-positive bacteria such as Staphylococcus aureus. The trans-δ-viniferin scaffold has multiple chemical functions and can therefore be modified in various ways to generate derivatives. Here we report the synthesis of 40 derivatives obtained by light isomerization, O-methylation, halogenation and dimerization of other stilbene monomers. The antibacterial activities of all generated trans-δ-viniferin derivatives were evaluated against S. aureus and information on their structure-activity relationships (SAR) was obtained using a linear regression model. Our results show how several parameters, such as the O-methylation pattern and the presence of halogen atoms at specific positions, can determine the antibacterial activity. Taken together, these results can serve as a starting point for further SAR investigations.