Inhibition of DNA Gyrase by Levofloxacin and Related Fluorine-Containing Heterocyclic Compounds

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Abstract

Fluoroquinolones are an important class of modern and efficient antibacterial drugs with a broad spectrum of activity. Levofloxacin (the optically active form of ofloxacin) is one of the most promising fluoroquinolone drugs, and its antibacterial activity is substantially higher than the activity of other drugs of the fluoroquinolone family. Earlier, in the Postovsky Institute of Organic Synthesis, UB RAS, an original method of levofloxacin synthesis was developed, and now the pilot batch of the drug is being prepared. Bacterial DNA gyrase is a specific target of fluoroquinolones; hence, the study of the enzyme-drug interaction is of theoretical and practical importance. Moreover, the parameters of DNA gyrase inhibition may serve as a criterion for drug quality. Here, we present the results of studying the interaction of DNA gyrase with a number of fluoroquinolones and their analogs: intermediates and semi-products of the levofloxacin synthesis, and also samples from the pilot batches of this drug. The importance of two structural elements of the levofloxacin molecule for the efficiency of the inhibition is revealed. The data obtained may be useful for the design of new drugs derived from levofloxacin.

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Inhibition of DNA Gyrase by Levofloxacin and Related Fluorine-Containing Heterocyclic Compounds
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About the authors

V L Tunitskaya

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

Email: ve_tun@mail.ru

A R Khomutov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

S N Kochetkov

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences

S K Kotovskaya

Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences; Urals Federal University

Yekaterinburg, Russia

V N Charushin

Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences; Urals Federal University

Yekaterinburg, Russia

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Copyright (c) 2011 Tunitskaya V.L., Khomutov A.R., Kochetkov S.N., Kotovskaya S.K., Charushin V.N.

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