Integrating utargeted metabolomics with biochemometrics to uncover antibacterial naphthyl derivatives in Guiera senegalensis leaves

Multidrug resistant bacteria (MDR) are one of the worldwide emerging threats to Public Health. S. epidermidis is a MDR pathogen and a major contributor to hospital-acquired infections, particularly due to its ability to form biofilms. Clinically, MDR S. epidermidis complicates treatment of device-associated infections and sepsis, requiring advanced diagnostics and therapies to mitigate its impact in healthcare settings [ 1 ]. Plant-derived natural products, due to their inherent chemical diversity, offer a promising avenue to address MDR [ 2 ]. Modern technologies are essential to revitalize ethnopharmacological tradition by accelerating the discovery pipeline [ 3 ]. In this study, we present the identification of anti-bacterial naphthyl derivatives from Guiera senegalensis leaves, used in different African countries to treat infectious and chronic diseases. Our combined approach of untargeted LC-HRMS and Molecular Networking-based metabolomics and NMR-based biochemometric analysis allowed both the comprehensive snapshot of the metabolome of the extract and the detection of key NMR-features responsible for the antibacterial activity exerted by the extract. NMR-fingerprint driven the chromatographic purification allowing the isolation of 7 naphthyl derivatives, including the new naphthyl-butenone guieranone C, and two unprecedented naphtho-γ-pirones, namely guierapyrone A and B. Isolated metabolites were tested for their anti-bacterial activity against S. epidermidis and oxacillin resistant S. epidermidis unveiling guieranone A as a good candidate for fighting staphylococcal infections. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany