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<p>Antimicrobial resistance is one of the most pressing global health challenges, as many pathogens are rapidly evolving to evade existing treatments. Despite this urgent need for new solutions, natural plant-derived compounds remain relatively underexplored in the development of antimicrobial drugs. This report highlights an innovative approach to discovering potent antimicrobial agents through bioguided fractionation of numerous plant species from the rich Argentinean flora. By systematically screening 60 species (over 177 extracts) for antimicrobial activity against representative strains of gram-positive and gram-negative bacteria, we identified promising bioactive compounds within the Asteraceae family—particularly sesquiterpene lactones from the <i>Xanthium</i> genus. Building on this basis, we synthesized semi-synthetic derivatives by chemically modifying plant sub-extracts, focusing on structures incorporating heteroatoms and/or heterocycles containing oxygen and nitrogen (important for the bioavailability and bioactivity that they are capable of providing). These modifications were evaluated for their potential to enhance antimicrobial efficacy against bacteria and <i>Candida</i> species, including resistant strains. Our findings suggest that tailoring natural metabolites from <i>Xanthium</i> and related Asteraceae species can significantly improve their antimicrobial properties. This strategy offers a promising pathway for the development of novel therapeutic agents to combat bacterial and fungal infections in an era of rising drug resistance.</p> Graphical Abstract <p></p>

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Rational search for natural antimicrobial compounds: relevance of sesquiterpene lactones

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月8日

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  • Alejandro Recio-Balsells,
  • Eugenia Rodriguez Ristau,
  • Adriana Pacciaroni,
  • Viviana Nicotra,
  • Carina Casero,
  • Manuela García

摘要

Antimicrobial resistance is one of the most pressing global health challenges, as many pathogens are rapidly evolving to evade existing treatments. Despite this urgent need for new solutions, natural plant-derived compounds remain relatively underexplored in the development of antimicrobial drugs. This report highlights an innovative approach to discovering potent antimicrobial agents through bioguided fractionation of numerous plant species from the rich Argentinean flora. By systematically screening 60 species (over 177 extracts) for antimicrobial activity against representative strains of gram-positive and gram-negative bacteria, we identified promising bioactive compounds within the Asteraceae family—particularly sesquiterpene lactones from the Xanthium genus. Building on this basis, we synthesized semi-synthetic derivatives by chemically modifying plant sub-extracts, focusing on structures incorporating heteroatoms and/or heterocycles containing oxygen and nitrogen (important for the bioavailability and bioactivity that they are capable of providing). These modifications were evaluated for their potential to enhance antimicrobial efficacy against bacteria and Candida species, including resistant strains. Our findings suggest that tailoring natural metabolites from Xanthium and related Asteraceae species can significantly improve their antimicrobial properties. This strategy offers a promising pathway for the development of novel therapeutic agents to combat bacterial and fungal infections in an era of rising drug resistance.

Graphical Abstract