carbadox and Bacterial-Infections

A series of novel 3,4-dihydropyrido[3,4-b]quinoxalin-1(2H)-one 5,10-dioxides was synthesized using an intramolecular amidation reaction. The lactams were screened in vitro and in vivo against Salmonella choleraesuis, Pasteurella multocida, and Escherichia coli. An N-methyl analogue was the most potent member of this series, with antibacterial activity comparable to that of the commercially important quinoxaline 1,4-dioxide carbadox.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Chemical Phenomena; Chemistry; Female; Lactams; Male; Mice; Microbial Sensitivity Tests; Quinoxalines; Salmonella

A Free-Wilson analysis of the antibacterial activity found in a variety of quinoxaline 1,4-dioxides prepared and tested in these laboratories unexpectedly predicted that potent activity should be found in the case where the heterocyclic ring system was substituted with an acetyl group in the 2 position and a hydroxymethyl group in the 3 position (2). The synthesis and antibacterial activity of this compound, which was actually isolated in the hemiketal form (3), and of several of its derivatives are reported. 1-Hydroxy-1-methyl-1,3-dihydrofuro[3,4-b]quinoxaline 4,9-dioxide (3) possesses exceptional activity in vivo against Escherichia coli, Salmonella choleraesuis, and Pasteurella multocida.

Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Female; Male; Mice; Microbial Sensitivity Tests; Quinoxalines; Structure-Activity Relationship