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

Abstract : The recent and persistent emergence of antibiotic-resistant bacterial strains, typically used clinically, is a serious public health problem. This is all the more accentuated by the misuse of antibiotics. It is therefore urgent to find new antibacterial targets and new antibacterial agents to fight against multidrug-resistant bacteria. To answer this problem, two strategies have been considered.The first strategy is used to identify and synthesize the new inhibitors of a histidine kinase (HK, a protein involved in the mechanism of resistance) as adjuvant antibiotics. Among the 47 synthesized compounds, two thiophene derivatives, two sulfonate derivatives and three sulphonamide derivatives less than 50 μM. These values have been improved compared to inhibitors synthesized in the laboratory. Besides, three furan derivatives inhibited the bacterial growth of both Gram-positive and Gram-negative bacteria. Finally, hydrochloric acid has an adjuvant activity of an antibiotic.The second study strategy, inhibiting the pathway of lysine biosynthesis, remained in the biosynthesis of peptidoglycan. This is possible by synthesis of unused amino acids based on triazole or alkyne, diaminopimelic acid (precursor of lysine). A total of 16 amino acids of the triazole type have been synthesized and their biological activities are in progress.
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Miyanou Rosales Hurtado. Approche pluridisciplinaire sur la problématique de la résistance bactérienne : conception, synthèse et évaluation de l’activité biologique de nouveaux agents antibactériens. Chimie thérapeutique. Université de Nîmes, 2019. Français. ⟨NNT : 2019NIME0003⟩. ⟨tel-02866461⟩

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