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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 <jats:italic>Candida<\/jats:italic> species, including resistant strains. Our findings suggest that tailoring natural metabolites from <jats:italic>Xanthium<\/jats:italic> 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.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s13659-025-00513-y","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T07:27:18Z","timestamp":1746689238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rational search for natural antimicrobial compounds: relevance of sesquiterpene lactones"],"prefix":"10.1007","volume":"15","author":[{"given":"Alejandro","family":"Recio-Balsells","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia Rodriguez","family":"Ristau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Pacciaroni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviana","family":"Nicotra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"Casero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6809-4723","authenticated-orcid":false,"given":"Manuela","family":"Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"513_CR1","unstructured":"Global antimicrobial resistance and use surveillance system (GLASS) report 2022. 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