Gyrase inhibition

Fig. 1.3 The increase in DNA gyrase inhibition activity (MNEC = maximum non-effective concentration in supercoiling assay) of weak indazole needle hit to optimised compound achieved...

The lack of direct proportionality between the MIC values and the gyrase inhibition values is suggested reasonably to be related to varying relative cell-penetrating properties of the different agents. Thus, enoxacin would appear... 

In another study concerning the conformational requirements of I-cyclopropyl-quinolones and their relationship to DNA gyrase inhibition, the conformation-ally constrained cyclopropane derivative (62), related to ofloxacin was prepared and evaluated in whole cells and for inhibition of DNA gyrase [95] the gem-dimethyl analogue (35), discussed earlier in the context of QSAR studies... 

Molecular Mechanisms of DNA Gyrase Inhibition by Quinolone Antibacterials Linus L Shen... 

Accordingly it appears that further QSAR investigations should focus separately on those parameters facilitating both cell wall penetration and those required for DNA gyrase inhibition. Then it should be possible to design structures which would maximize both responses. 

Alnumycin, an aromatic polyketide antibiotic, contains a sugar-like 4-hydroxymethyl-5-hydroxy-l,3-dioxan moiety and was isolated in 1998 from Streptomyces sp. DSM 11575 and Streptomyces griseorubiginous strain MerKl 115 [385, 386], It exhibits a variety of biological activities such as antibiotic, cytostatic, gyrase inhibition, and... 

DNA topoisomerase inhibited by anticancer DNA gyrase inhibited by antibacterial drugs, e.g. drugs, e.g. etoposide fluoroquinolones... 

The enzymes gyrase and topoisomerase IV can be protected from fluoroquinolone inhibition by a small protein belonging to the pentapeptide-repeat family of... 

Simon, H., L. Kittler, E. Baird, P. Dervan, and C. Zimmer Selective inhibition of DNA gyrase in vitro by a GC specific eight-ring hairpin polyamide at nanomolar concentration. FEBS Lett. 2000, 471, 173-176. 

Chromosome function Quinolones Metronidazole (also ) Nitrofu rantoin Rifampicin (also ) 5-Fluorocytosine Inhibit DNA gyrase DNA strand breakage DNA strand breakage Inhibits RNA polymerase Inhibits DNA synthesis No action on mammalian equivalent Requires anaerobic conditions not present in mammalian cells No action on mammalian equivalent Converted to active form in fungi... 

F luoro qu i nolones Norfloxacin Inhibits topoisomerase 11 (DNA gyrase). Gram-negative organisms, including... 

The answer is d. (Hardman, pp 1065—1067. Katzung, p 797.) Bacterial DNA gyrase is composed of four subunits, and levofloxacin binds to the strand-cutting subunits, inhibiting their activity... 

Figure 6.2. Proposed model for quinolone-DNA cooperative binding in the inhibition of DNA gyrase [32], (Reprinted with permission American Chemical Society.)...

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