Synthesis and antibacterial activity of some 3-[(alkylthio)methyl]quinoxaline 1-oxide derivatives.

Some 3-[(alkylthio)methyl]quinoxaline 1-oxide derivatives (1) have been synthesized and screened for antibacterial activity. 2-Acetyl-3-[(methylsulfonyl)methyl]quinoxaline 1-oxide (7a) was found to possess good in vitro activity against some pathogens important to veterinary medicine including Treponema hyodysenteriae, a causative agent in swine dysentery. In an in vivo experiment, this compound (7a) completely protected pigs against a swine dysentery challenge over a 21-day period.

Pyridoquinoxaline N-oxides. 2. Synthesis and antibacterial activity of tricyclic lactams.

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.

Synthesis and antibacterial activity of 1-hydroxy-1-methyl-1,3-dihydrofuro[3,4-b]quinoxaline 4,9-dioxide and related compounds.

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.

Mode of action of a structurally novel beta-lactam.

CP-35,587 {6-[d-2-amino-2-(p-hydroxyphenyl)acetamido]-2,2-dimethyl-3- (5-tetrazolyl)-penam} is a member of a new family of beta-lactam antibacterial agents. Because the biospectrum of CP-35,587 has features similar to both penicillins and cephalosporins, experiments were carried out to explore its mode of action. CP-35,587 did not inhibit peptidoglycan transpeptidase from Escherichia coli, but it did inhibit dd-carboxypeptidase.

Synthesis and antibacterial activity of isomeric 6- and 7-acetyl-3-methyl-2- quinoxalinecarbozamide 1,4-dioxides.

The synthesis, separation, and structure determination of 6- and 7-acetyl--3-methyl-2-quinoxalinecarboxamide 1,4-dioxides are reported together with a comparison of their antibacterial activity. The structural assignment of these 6- and7-acetyl isomers was based on NMR analysis of related mono-N-oxide derivatives, which were obtained by treatment of the quinoxaline 1,4-dioxides with acetic anhydride--acetic acid or trimethyl phosphite. The compounds were screened for in vitro and in vivo activity against Escherichia coli, Salmonella choleraesuis, Pasteurella multocida, and Streptococcus pyogenes.

DD-carboxypeptidase and peptidoglycan transpeptidase from Pseudomonas aeruginosa.

Peptidoglycan transpeptidase and dd-carboxypeptidase have been detected in isolated membranes of Pseudomonas aeruginosa. Cephalosporins and penicillins fail to inhibit the transpeptidase at concentrations as high as 100 mug/ml. dd-Carboxypeptidase, on the other hand, is sensitive to inhibition by beta-lactam antibiotics.