University System of Maryland

Erik De Leeuw

Alexander D MacKerell, Jr

Steven Fletcher

Alexander MacKerell

Jamal Chauhan

Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a generic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compound 6jc48-1 ((E)-2,4-bis(4-bromophenyl)-6-(4-(dimethyl-amino)styryl)pyrylium boron tetrafluoride salt) binds to Lipid II with high affinity, has markedly reduced cytotoxicity than BAS00127538, and retains activity against drug-resistant strains of. It is stable in plasma, has dramatically improved pharmacokinetic and pharmacodynamics properties, and possesses in vivo efficacy in a mouse model of sepsis. 

Small molecule lipid II inhibitors

Newly synthesized derivatives of BAS00127538 have been discovered to possess antibiotic activity and to combat resistant bacterial strains. Compounds and pharmaceutical compositions containing these compounds are described, and are based on a genetic scaffold structure. Synthetic methods and methods of using the compounds also are described. Preferred compounds bind to Lipid II with high affinity, have markedly reduced cytotoxicity compared to BAS00127538, and retain activity against drug-resistant strains of Enterococci. They are stable in plasma, have dramatically improved pharmacokinetic and pharmacodynamics properties, and possess in vivo efficacy in a mouse model of sepsis. 

Disclosed are compositions and methods for treating and/or preventing infections in mammals, by administering to a mammal a therapeutically effective amount of at least one defensin-like molecule, e.g., in a composition that includes such molecule. Also disclosed are kits that include such molecules, or compositions that include such molecules, as well as instructions for using such molecules to treat a mammal.

Defensin-like molecules as novel antimicrobial agents

Disclosed are methods of treating and/or preventing infections in mammals caused by microorganisms, by administering to a mammal a therapeutically effective amount of at least one defensin-like molecule, e.g., in a composition that includes such molecule. Also disclosed are the use of such defensin-like molecules for treating and/or preventing infections in mammals; and kits that may include such molecules, or compositions that include such molecules, as well as instructions for using such molecules to treat a mammal.

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Baltimore, MD, United States of America

Erik De Leeuw