University of Notre Dame Du Lac

Hsiri Therapeutics, Inc.

Patricia Miller

Marvin J Miller

Cheng Ji

Yun-Ming Lin

Manuka Ghosh

Ute Möllmann

Serena Carosso

Rui Liu

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic &#x3b2;-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized &#x3b1;-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity-relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains ofwhich have been listed by the WHO as being of critical concern worldwide.

Antibacterial monobactams

A compound, comprising: an Fe(III)-binding and/or Fe(III)-bound siderophore; one or more optional linker covalently bound to the siderophore; and daptomycin covalently bound to the linker, or, if no linker is present, then to the siderophore; or pharmaceutically acceptable salt or solvate thereof.

Antibacterial sideromycins

An artificial tris-catecolate siderophore with a tripodal backbone and its conjugates with ampicillin and amoxicillin were synthesized. Both conjugates exhibited significantly enhanced in vitro antibacterial activities against Gram-negative species compared to the parent drugs, especially against. The conjugates appear to be assimilated by an induced bacterial iron transport process as their activities were inversely related to iron concentration. The easily synthesized tris-catecolate siderophores can be used with a variety of drugs as conjugates to target antibiotic-resistant Gram-negative bacteria.

Anti-bacterial siderophore-aminopenicillin conjugates

Growing community of inventors

South Bend, IN, United States of America

Patricia Miller