BREAUD Célia's thesis “New strategy in the search for natural anti-tuberculosis agents derived from the flora of French Guyana”.”

Mrs. BREAUD Célia, doctoral student at IMBE, team Functional ecology: from socio-ecological systems to molecules, will publicly defend his thesis on Monday 15 December 2025 at 2pm in the Thesis Room of the Faculty of Pharmacy.

In front of a jury made up of :

• Sophie TOMASI,Rapporteur and Chair of the Jury, Professor, University of Rennes
• Mehdi BENIDDIR, Professor, University of Paris-Saclay
• Gaëtan HERBETTE, Examiner, Research Engineer, Université Paris-Saclay
• Stéphane CANAAN,Examiner, Research Director, University of Aix-Marseille
• Sok-Siya BUN-LLOPET, PhD supervisor, University Professor - Hospital Practitioner, University of Aix-Marseille
• Elnur GARAYEV, PhD thesis co-director, Senior Lecturer, University of Aix-Marseille

Summary of work:

Tuberculosis remains a major public health issue, reinforced by the emergence of resistant strains. In this context, this thesis explores the flora of French Guyana as a source of metabolites with anti-tuberculosis potential, combining biological screening, metabolomics by LC-MS/MS and molecular network analysis, with integration of activity data.

The first phase focused on seven species selected on the basis of ethnopharmacological and phytochemical criteria. The extracts and fractions were tested against Mycobacterium tuberculosis H37Ra, then profiled by LC-HRMS/MS. Molecular networks were used to link chemical families and activity levels, prioritise candidates and rapidly dereplicate known compounds, while revealing anti-tuberculosis compounds in several active extracts.

The second part focused on two species of the genus Aspidosperma (Apocynaceae), rich in monoterpene indole alkaloids. Bioguided fractionation, coupled with molecular networks, revealed a core of compounds correlated with the inhibition of M. tuberculosis. The results support the interest of this chemical reservoir, while highlighting the need for targeted isolations and structural validation by NMR to finely attribute the activity.

The third part dealt with Lantana trifolia (Verbenaceae). Fractions of intermediate polarity were found to be the most active, and metabolomic analysis indicated the possible contribution of a small group of abundant metabolites to activity. Global annotation also confirmed a profile rich in flavonoids, phenolic acids and glycosylated phenylpropanoids, suggesting a cumulative or synergistic effect consistent with the distribution of activity observed.

Methodologically, the thesis demonstrates the value of a reproducible pipeline combining high-resolution LC-MS/MS, automated dereplication and bioactive molecular networks to rationalise the prioritisation of fractions and guide isolation. From a scientific point of view, it documents the chemodiversity of as yet little-studied Amazonian species, establishes clear links between chemical families and antimycobacterial response, and highlights priority molecular groups.

Taken together, this work demonstrates the contribution of integrated metabolomic approaches to exploiting tropical bioresources in the fight against Mycobacteium tuberculosis. They provide a body of analytical and biological data that can be directly mobilised for targeted isolation, pharmacological evaluation and local resource development, in line with an ethical and partnership-based approach to bioprospecting in French Guiana.