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Article Dans Une Revue International Journal of Molecular Sciences Année : 2023

6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens

Katy Jeannot
Jean Michel Brunel

Résumé

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n, and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f, which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance.
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Dates et versions

hal-04161494 , version 1 (20-07-2023)

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Delphine Vergoz, Flore Nilly, Florie Desriac, Magalie Barreau, Antoine Géry, et al.. 6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens. International Journal of Molecular Sciences, 2023, 24 (10), pp.8568. ⟨10.3390/ijms24108568⟩. ⟨hal-04161494⟩
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