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

受阳离子肽启发的氨基烷基白藜芦醇衍生物的合成及抗菌活性

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作者:Rubén Cebrián, Ricardo Lucas, María Victoria Fernández-Cantos, Koen Slot, Pablo Peñalver, Marta Martínez-García, Antonio Párraga-Leo, María Violante de Paz, Federico García, Oscar P Kuipers, Juan Carlos Morales

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.

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