Synthesis and antibacterial activity of thiazolo-, oxazolo-, and imidazolo[3,2-a][1,8]naphthyridinecarboxylic acids.
It is known that thiazolo[3,2-a][1,8]naphthyridine derivatives (3a) exhibit good antibacterial activity. Accordingly, several analogues of 3a, viz. oxazolo- and imidazolo[3,2-a][1,8]naphthyridine derivatives 3b and 3c, were synthesized and evaluated for antibacterial activity in vitro and for inhibitory activity against DNA gyrase of Escherichia coli K-12 C600. Compound 3a exhibited antibacterial activity comparable to that of ofloxacin and enoxacin against Gram-positive and Gram-negative bacteria and displayed antibacterial activity superior to that of 3b and 3c. The antibacterial activities of 3b and 3c decreased in that order. DNA gyrase inhibitory activities of 3a-c in E. coli K-12 C600 paralleled their in vitro antibacterial activity. It was found that enhancement of the DNA gyrase inhibitory activity of 3a was dependent on a certain feature of the sulfur atom of the thiazole ring.
Kondo
H
H
Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
Taguchi
M
M
Inoue
Y
Y
Sakamoto
F
F
Tsukamoto
G
G
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D004926:Escherichia coli / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
D000900:Anti-Bacterial Agents; D007093:Imidazoles; D007202:Indicators and Reagents; D009287:Naphthyridines; D010080:Oxazoles; D013844:Thiazoles; D059005:Topoisomerase II Inhibitors