Synthesis and antimicrobial activity of aminoalkyl resveratrol derivatives inspired by cationic peptides

Abstract

Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.

Graphical abstract

Keywords:

• Resveratrol
• aminoalkyl
• membrane permeabilization
• antimicrobial
• anaerobic bacteria
• synergism
• toxicity
• haemolysis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Junta de Andalucía [FQM-7316] and the Dutch Research Council [NWA-Idea Generator project NWA.1228.191.006]. Rubén Cebrián was supported by the Ramon- Areces Foundation and the NWO-NACTAR program. Ricardo Lucas was supported by a TalentHub contract from Junta the Andalucía-EC program. The following reagents were obtained through BEI Resources, NIAID, NIH: Bacteroides ovatus 3_8_47FAA and Parabacteroides merdae CL03T12C32.