Article thumbnail
Location of Repository

Biological characterization of cyclothialidine, a new DNA gyrase inhibitor.

By N Nakada, H Shimada, T Hirata, Y Aoki, T Kamiyama, J Watanabe and M Arisawa

Abstract

Cyclothialidine is a new DNA gyrase inhibitor isolated from Streptomyces filipinensis NR0484. Structurally, it belongs to a new class of natural products containing a unique 12-membered lactone ring that is partly integrated into a pentapeptide chain. Cyclothialidine was found to be one of the most active of all the DNA gyrase inhibitors tested in the DNA supercoiling reaction of Escherichia coli DNA gyrase; 50% inhibitory concentrations (in micrograms per milliliter) of 0.03 (cyclothialidine), 0.06 (novobiocin), 0.06 (coumermycin A1), 0.66 (norfloxacin), 0.88 (ciprofloxacin), and 26 (nalidixic acid) were found. In addition, DNA gyrases from gram-positive species were inhibited equally as well as DNA gyrase from E. coli. Cyclothialidine also inhibited the in vitro DNA replication directed from oriC of E. coli. Among the bacterial species tested, only Eubacterium spp. were inhibited by cyclothialidine, suggesting that it can enter the cells of Eubacterium and exert antibacterial activity through interference with the DNA gyrase within the cells, although its penetration into most bacterial cells appears to be poor. These results provide a basis for cyclothialidine to be a lead structure for novel antibacterial agents with DNA gyrase inhibitory activities

Topics: Research Article
Year: 1993
DOI identifier: 10.1128/aac.37.12.2656
OAI identifier: oai:pubmedcentral.nih.gov:192769
Provided by: PubMed Central
Sorry, our data provider has not provided any external links therefore we are unable to provide a link to the full text.

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.