Email this article Inhibition of DNA Gyrase by Levofloxacin and Related Fluorine-Containing Heterocyclic Compounds
- Authors: Tunitskaya VL1, Khomutov AR1, Kochetkov SN1, Kotovskaya SK2,3, Charushin VN2,3
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Affiliations:
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences
- Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences
- Urals Federal University
- Issue: Vol 3, No 4 (2011)
- Pages: 94-99
- Section: Articles
- URL: https://actanaturae.ru/2075-8251/article/view/10660
- DOI: https://doi.org/10.32607/20758251-2011-3-4-94-99
- ID: 10660
Cite item
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.
Full Text
Inhibition of DNA Gyrase by Levofloxacin and Related Fluorine-Containing Heterocyclic Compounds×
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 UniversityYekaterinburg, Russia
V N Charushin
Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences; Urals Federal UniversityYekaterinburg, Russia
References
- The New Generation of Quinolones. / Eds Siporin C., Heifetz C.L., Domagala J.M. 1990. 422 p.
- Shen L.L. Quinolone Antibacterial Agents. Washington: American Soc. Microbiol., 1993. 344 p.
- Quinolone Antimicrobial Agents. / Eds Hooper D.S., Wolfson J.S. 1993.
- Padeyskaya E.N., Yakovlev V.P. // Fluoroquinolones Moscow: Bioinform, 1995. 208 p.
- Mokrushina G.A., Charushin V.N., Chupakhin O.N.// Pharmaceutical Chemistry Journal, 1995. № 1. P. 5-19.
- Ball P. The Quinolones. / Ed. Andriole T.V. San Francisco: Acad. Press, 1998. P. 1-28.
- Mokrushina G.A., Nosova E.N., Lipunova G.N., Charushin V.N. // Russian Journal of Organic Chemistry 1999. V. 35. № 10. P. 1447-1462.
- Granik V.G. // Basic Medicinal Chemistry Moscow: Vuzovskaya Kniga, 2001.
- Furin G.G. // Fluorine-containing Heterocyclic compounds: Synthesis and Applications Novosibirsk:Nauka, 2001.
- Mokrushin V.P., Vavilov G.A. // Principles of the Chemistry and technology of bioorganic and synthetic medical preparations. Ekaterinburg: UGTU-UPI, 2004.
- Nosova E.V., Mochulskaya N.N., Kotovskaya S.K., Lipunova G.N., Charushin V.N. // Heteroatom. Chemistry. 2006. V. 17. № 6. Р. 579-586
- Yakovlev V.P., Yakovlev S.V. // Infections and Antimicrobial therapy 2004. V. 6. № 4. (http://old.consilium-medicum.com/ media / infektion/04_04/108.shtml )
- Hayakawa I., Atarashi S., Yokohama S., Imamura M., Sakano K., Furukawa M. // Antimicrob. Agents Chemother. 1986. V. 29. №1. Р. 163-164.
- Krasnov V.P., Levit G.L., Korolyova M.A., Kodess M.I., Chupakhin O.N., Kim M.H., Lee H.S., Park Y. J., Kim K.-C. // Tetrahedron: Asymmetry, 1999. V. 10. P. 2691-2702.
- Japanese Patent JP 2000178265. Production of (S)-benzoxazine derivative and racemization of (R)-benzoxazine derivative. / Chupakhin O.N., Krasnov V.P., Levit G.L., Charushin V.N., Korolyova M.A., Tzoi E.V., Lee H.S., Park Y.J., Kim M.H., Kim K.Ch.; publication date 27.06.2000 (Chem. Abstr., 2000. V. 133. P. 43530).
- Krasnov V.P., Levit G.L., Bukrina I.M., Andreeva I.N., Sadretdinova L.Sh., Korolyova M.A., Kodess M.I., Charushin V.N., Chupakhin O.N. // tetrahedron: Asymmetry, 2003. V. 14. P. 1985-1988.
- Potemkin V.A., Krasnov V.P., Levit G.L., Bartashevich E.V., Andreeva I.N., Kuzminsky M.B., Anikin N.A., Charushin V.N., Chupakhin O.N. // Mendeleev Comm. 2004. P. 69-71.
- Krasnov V.P., Levit G.L., Kodess M.I., Charushin V.N., Chupakhin O.N. // Tetrahedron: Asymmetry. 2004. V. 15. № 5. P. 859-862.
- Gruzdev D.A., Levit G.L., Krasnov V.P., Chulakov E.N., Sadretdinova L.Sh., Grishakov A.N., Ezhikova M.A., Kodess M.I., Charushin V.N. // Tetrahedron: Asymmetry. 2010. V. 21. P. 936-942.
- Levit G.L., Gruzdev D.A., Krasnov V.P., Chulakov E.N., Sadretdinova L.Sh., Ezhikova M.A., Kodess M.I., Charushin V.N. // Tetrahedron: Asymmetry. 2011. V. 22. P. 185-189.
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