Disease relevance of C12057

• The mechanism of inhibition of DNA gyrase by cyclothialidine, a novel gyrase inhibitor isolated from Streptomyces filipinensis NR0484, has been studied further by using [14C]benzoylcyclothialidine and a reconstituted Escherichia coli gyrase system consisting of the A subunit, the B subunit and relaxed ColE1 DNA [1].
• Cyclothialidine is a new, potent DNA gyrase inhibitor isolated from Streptomyces filipinensis [2].
• Congeners of cyclothialidine were found to exhibit a moderate, but broad-spectrum, in vitro activity against Gram-positive bacteria [2].
• GyrB mutations in Staphylococcus aureus strains resistant to cyclothialidine, coumermycin, and novobiocin [3].
• 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 [4].

High impact information on C12057

• Characterization of the binding site for cyclothialidine on the B subunit of DNA gyrase [1].
• Therefore, the DNA gyrase inhibitory principle contained in cyclothialidine can be considered as the basis for a new class of antibacterial agents [2].
• Cyclothialidine competitively inhibited the ATPase activity of DNA gyrase (Ki = 6 nM) [5].
• Cyclothialidine also inhibited the in vitro DNA replication directed from oriC of E. coli [4].
• Cyclothialidine inhibited Escherichia coli DNA gyrase with an IC50 of 30 ng/ml [6].

Chemical compound and disease context of C12057

• We investigated how cyclothialidine (Ro 09-1437), a novel DNA gyrase inhibitor belonging to a new chemical class of compounds, acts to inhibit Escherichia coli DNA gyrase [5].

References