Approche pluridisciplinaire de la problématique de la résistance bactérienne : conception, synthèse, évaluation de l'activité biologique et de la biodégradabilité de nouveaux agents antibactériens

Abstract : Over the two past decades, the massive use of antibiotics has led to the emergence of resistant bacterial strains against most families of antibiotics available on the pharmaceutical market. The emergence of multiresistant and totoresistant bacterial strains particularly in hospitals, which create increasing problem in the development of new therapeutics and constitutes serious public health threat problems. During my PhD, two approaches were discussed.The first approach of this project consist in targeting the DapF and MurE enzymes, which are implicated in the biochemical pathway for peptidoglycan biosynthesis, a key component of the bacterial cell wall. Consequently, we prepared amino acids derivatives with triazolyl and alkynyl groups, sterically hindered analogs of 2,6-diaminopimelic acid (meso-DAP).The second approach is the development of antibiotic adjuvants, to target specific proteins implicated in the development of bacterial resistance mechanisms (Histidine kinases, HKs). This work has enabled the development of thirty-three thiophene derivatives, eight of them have biological activity against three HKs (1.63 < IC50 (μM) < 243.9). In addition, among the eight molecules with biological activity, two of them present inhibition of bacterial growth (bactericide) against both gram-positive and/or gram-negative bacteria (B. subtilis, S. aureus, B. anthracis, E. coli…) and one of them restores the sensibility of bacterial strains (E. coli producing extended spectrum of β-lactamases (ESBL) and S. aureus resistant to methicillin (MRSA)) to the appropriate antibiotic (cefotaxim).
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-01681283
Contributor : Abes Star <>
Submitted on : Thursday, January 11, 2018 - 4:01:09 PM
Last modification on : Tuesday, February 20, 2018 - 10:34:08 AM

File

74457_BOIBESSOT_2016_archivage...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-01681283, version 2

Collections

Citation

Thibaut Boibessot. Approche pluridisciplinaire de la problématique de la résistance bactérienne : conception, synthèse, évaluation de l'activité biologique et de la biodégradabilité de nouveaux agents antibactériens. Chimie thérapeutique. Université de Nîmes, 2016. Français. ⟨NNT : 2016NIME0002⟩. ⟨tel-01681283v2⟩

Share

Metrics

Record views

196

Files downloads

115