Calixarenes, highly organized molecular platforms with high structural modulation potential, allow the development of structures capable of multivalent binding to a biological target (bacteria, viruses, cells) via custom-designed patterns.
In this way, we are designing new anti-infective agents based on a calixarenic structure; the synthetic methods developed in the laboratory have led to the development of new poly-ionic calixarenes, several of which are proving to be very good antibacterial, anti-mycobacterial (lead compound CX1) and antiviral candidates.
We also value the organizational platform character of these macrocycles in the design and development of antibacterial prodrugs with synergistic activity (two active ingredients with different action sites, for example inhibition of peptidoglycan synthesis and DNA gyrase) or antivirals, with a particular interest in studying their behavior on biological membrane models (Langmuir balances).
Another aspect concerns the development of bacteriophilic and potentially antibacterial materials, by transposing the antibacterial activity of our active molecules onto polymeric supports.
Our work deals with a « reprofiling » strategy. This approach which is emerging in the pharmaceutical industry, consists in searching for new applications to existing drugs. In this context, we are working on troglitazone (TGZ) which was used for diabetes treatment, but also showed interesting anti-proliferative properties towards various cancerous cell lines.
Preliminary structure-activity relationships on the TGZ core revealed major modifications increasing its activity towards cancerous cells and/or decreasing its toxicity towards normal cells.
In a joint effort with Axe 1 (C. Comoy), we are conducting methodologic studies in order to build selective modifications on both heterocycles: the chromane on the one hand, and the benzylidenethiazolidine-2,4-dione on the other hand. This will allow their optimisation on both activity and toxicity aspects.
The anti-cancerous activity of these compounds is being studied in collaboration with researchers at CRAN laboratory (UMR 7039, Université de Lorraine). A special attention is devoted to cellular events induced by our compounds.
One of our molecules is under development in collaboration with SATT Grand Est (SAYENS).
In vivo synthesis of biomolecules: Study of plant/endophyte interactions
A) in vivo synthesis methods of galanthamine and lycorin, two Amaryllidaceae alkaloids of pharmaceutical and biological interest, very difficult to access synthetically (Eng. Life Sci., 2016, 16(8), 731-739).
B) methods for identifying endophytic fungi and the study of the biological activities of extracts from these endophytes (FEMS Microbiology Letters, 2016, 363(11), fnw089).
Currently our research is based on the study of interactions between plants and endophytes and its objectives are to identify new bioactive compounds with high added value.
Endophytic microorganisms are associated with plants and colonize the internal tissues of the plant. A complex molecular dialogue between these two entities can modulate plant growth and stress tolerance, which will lead to the production of highly diverse specialized metabolites.
We will focus on the interaction between plants of the Amaryllidaceae family and the endophytes they contain (LUE project: Biomolecular IMPACT).
Tracers and Ligands for molecular imaging
We develop functionalization methods of carbohydrate derivatives (NPM, SLL) as well as peptidic and macrocyclic ligands (KS) studied for their metal complexation properties.
One of the main application field of these systems is molecular imaging (PET Positron Emission Tomography). These works aim at designing bi-functional tools bearing an arm for the anchoring of a bioactive peptide and affording the possibility to introduce a radioactive atom by covalent bond (F) or by coordination (Cu, Ga).
The saccharidic prosthetic groups allow an easy introduction of fluorine-18 and are conjugated with a bioactive peptide by click reaction. One application is angiogenesis and tumor imaging.
According to the multiple functionalities of carbohydrate derivatives, dual dyes equipped with a radioisotope and a fluorophore are developed for bimodal molecular imaging (PET/ near IR fluorescence, ANR M3ODALITy).
Based on our expertise in metal complexation chemistry, we develop novel macrocyclic systems with triazolyl moieties as metal coordinating pendant arms.
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