Synthesis and antibacterial activity of thiazolo-, oxazolo-, and imidazolo[3,2-a][1,8]naphthyridinecarboxylic acids

J Med Chem. 1990 Jul;33(7):2012-5. doi: 10.1021/jm00169a033.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Escherichia coli / enzymology
  • Gram-Negative Bacteria / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology
  • Indicators and Reagents
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Naphthyridines / chemical synthesis*
  • Naphthyridines / pharmacology
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology
  • Topoisomerase II Inhibitors

Substances

  • Anti-Bacterial Agents
  • Imidazoles
  • Indicators and Reagents
  • Naphthyridines
  • Oxazoles
  • Thiazoles
  • Topoisomerase II Inhibitors