The synthesis of a series of D-gluco-like configured 4,5,6-trihydroxyazepanes bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is described. These synthetic derivatives have been tested for their ability to selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby increase sensitivity of Pseudomonas aeruginosa to β-lactams, a pathway with substantial therapeutic potential. While introduction of triazole and sulfamide groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to be a selective inhibitor of NagZ over other glucosaminidases including human OGA and lysosomal hexosaminidases HexA and B.
The synthesis of a series of D-gluco-like configured
4,5,6-trihydroxyazepanes bearing a triazole, a sulfonamide or a fluorinated
acetamide moiety at C-3 is described. These synthetic derivatives have been
tested for their ability to selectively inhibit the muropeptide recycling
glucosaminidase NagZ and to thereby increase sensitivity of Pseudomonas
aeruginosa to β-lactams, a pathway with substantial therapeutic potential.
While introduction of triazole and sulfamide groups failed to lead to
glucosaminidase inhibitors, the NHCOCF3 analog proved to be a selective
inhibitor of NagZ over other glucosaminidases including human OGA and
lysosomal hexosaminidases HexA and B