Metabolomic landscape of Helianthus annuus hybrid seeds feeds the cheminformatic discovery of K. pneumoniae MrkH quorum sensing inhibitors

Sunflower ( Helianthus annuus ) seeds are underexplored, yet phytochemical-rich, with many potential health benefits. H. annuus -based metabolites could also be channeled toward the search for novel quorum sensing inhibitors (QSIs), a new class of antimicrobials. Hence, this study modelled sunflower hybrid seeds metabolites against the key QS system protein (MrkH) of Klebsiella pneumoniae , a critical priority pathogen requiring novel therapeutics. Following the metabolomic profiling of hybrid seed extracts, H. annuus metabolites were modelled against the MrkH protein using advanced computational methods. Molecular docking revealed best binding poses for 5 lead metabolites (calceolarioside A, dicaffeoyl quinic acid, guanosine, cynarin, xanthosine) with a docking score range of -8.8 to -7.8 kcal/mol, relative to the autoinducer (-5.8 kcal/mol). Pharmacokinetics revealed that guanosine and xanthosine are explorable within the Lipinski rule of 5 (LRo5), and other leads beyond the Ro5. Dynamics simulation showed that all leads had higher negative binding free energy (ΔG bind ) in the range -42.54 kcal/mol (dicaffeoyl quinic acid) to -28.67 kcal/mol (guanosine) compared to the autoinducer (-10.85 kcal/mol) and cinnamaldehyde standard (-15.88 kcal/mol). All leads had stable interactions with MrkH active site residues (Arg106, Arg107, Asp109, Arg111, Asn183, Gln201, Ser140). Lead ligands-MrkH complexes were thermodynamically stable and compact, with increased number of hydrophobic and hydrogen bond interactions. The lead metabolites from H. annuus hybrid seeds could be explored as new MrkH QS system inhibitors after conducting further in vivo and in vitro validation steps. Sunflower seeds thus hold significant potentials for drug discovery and therapeutics development, among other possible industry applications. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany