Planta Med 2023; 89(14): 1289
DOI: 10.1055/s-0043-1773847
Abstracts
Monday 3rd July 2023 | Short Lecture Session A
Metabolomics/Molecular networking/Chemometrics/Profiling/AI

Short Lecture "Targeted isolation of new anti-infective natural products through multi-informative metabolite networks and HPLC-based bioactivity profiling using a 3R infection model"

Olivier Kirchhoffer
1   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU,1206, Geneva, Switzerland
2   School of Pharmaceutical Sciences, University of Geneva, CMU, 1206, Geneva, Switzerland
,
Jahn Nitschke
3   Department of Biochemistry, Faculty of Sciences, University of Geneva, Quai Ernest-Ansermet 30, 1205 Geneva, Switzerland
,
Louis-Félix Nothias
1   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU,1206, Geneva, Switzerland
2   School of Pharmaceutical Sciences, University of Geneva, CMU, 1206, Geneva, Switzerland
,
Nabil Hanna
3   Department of Biochemistry, Faculty of Sciences, University of Geneva, Quai Ernest-Ansermet 30, 1205 Geneva, Switzerland
,
Laurence Marcourt
1   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU,1206, Geneva, Switzerland
2   School of Pharmaceutical Sciences, University of Geneva, CMU, 1206, Geneva, Switzerland
,
Pierre-Marie Allard
4   Department of Biology, University of Fribourg, Rue A.-Gockel 3, 1700 Fribourg, Switzerland
,
Antonio Grondin
5   5 Pierre Fabre Research Institute, Green Mission Department, Herbal Products Laboratory, 31035 Toulouse, France
,
Emerson Ferreira Queiroz
1   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU,1206, Geneva, Switzerland
2   School of Pharmaceutical Sciences, University of Geneva, CMU, 1206, Geneva, Switzerland
,
Thierry Soldati
3   Department of Biochemistry, Faculty of Sciences, University of Geneva, Quai Ernest-Ansermet 30, 1205 Geneva, Switzerland
,
Jean-Luc Wolfender
1   Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, CMU,1206, Geneva, Switzerland
2   School of Pharmaceutical Sciences, University of Geneva, CMU, 1206, Geneva, Switzerland
› Institutsangaben
› Weitere Informationen
Auch verfügbar aufeRef
 
 

    Mycobacterium tuberculosis (Mtb), along with the looming threat of Multidrug-Resistant Tuberculosis (MDR-TB), provide a strong incentive nowadays to extend beyond the scope of known TB antibiotics. To find new anti-infective compounds, we used an innovative 3R infection model system consisting of Mycobacterium marinum as a surrogate for Mtb and the amoeba Dictyostelium discoideum as a surrogate for macrophages. This host-pathogen system offers a double readout that allows us to evaluate a compound with regards to its activity on the host and the pathogen. In addition to that, a large chemodiverse set of 1600 plant part extracts was established and analysed through untargeted High Resolution tandem Mass Spectrometry (HRMS/MS) experiments. After different steps of assay optimisation (notably throughput improvements), the whole extract library was screened for anti-infective activities. Combining the results with metabolomics analysis yielded a prioritised subset of extracts to work on. In order to rapidly identify bioactive compounds, chosen extracts were taken through a process of High- resolution HPLC-based bioactivity profiling. Metabolite annotations of the fractions generated allowed for the targeted isolation of compounds of interest, while discarding already reported or pan-assay interference compounds (PAINS) at an early stage. Using this approach, a total of 53 compounds could be isolated from 13 different plants, 22 of which displayed previously unreported anti-infective activity. The workflow was partially automated and generic conditions were established, to enable rational characterisation of active principles in a given plant set, usually within a few weeks ([Fig. 1]).

    Zoom
    Fig. 1 General workflow used for the isolation and characterization of new anti-infective compounds.

     

    Publikationsverlauf

    Artikel online veröffentlicht:
    16. November 2023

    © 2023. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Rüdigerstraße 14, 70469 Stuttgart, Germany

     
    Zoom
    Fig. 1 General workflow used for the isolation and characterization of new anti-infective compounds.