6-Polyaminosteroid Squalamine Analogues Display Antibacterial Activity against Resistant Pathogens

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Vergoz, Delphine | Nilly, Flore | Desriac, Florie | Barreau, Magalie | Géry, Antoine | Lepetit, Charlie | Sichel, François | Jeannot, Katy | Giard, Jean-Christophe | Garon, David | Chevalier, Sylvie | Muller, Cécile | Dé, Emmanuelle | Brunel, Jean, Michel

Edité par CCSD ; MDPI -

International audience. 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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