Advertisement

N-Pyridyl-Substituted Carboxypiperidine Amides: A New Class of Prokaryote Translation Inhibitors

  • Ya. A. Ivanenkov
  • E. S. Komarova (Andreyanova)
  • I. A. Osterman
  • P. V. Sergiev
  • R. S. Yamidanov
  • E. V. DeinekaEmail author
  • V. A. Terent’ev
  • G. I. Fil’kov
  • A. A. Sofronova
  • A. G. Mazhuga
  • O. A. Dontsova
Article

High-throughput screening identified a new class of antibacterial compounds based on N-pyridyl-substituted p- and m-carboxypiperidine amides. Constructs with the two reporter genes RFP and Katushka2S allowed the detection of compounds that inhibit protein translation against DNA biosynthesis. Some agents of this class demonstrated antibacterial activity by inhibiting translation. The most promising compound had an MIC of 12 μg/mL. Thus, this class could become a valuable platform for developing new compounds with higher antibacterial activity and selectivity.

Keywords

bacteria antibiotic ribosome screening reporter 

Notes

Acknowledgments

The work was financially supported by the Ministry of Education and Science of the Russian Federation, Government Grant 20.9907.2017/VU (expert opinion, discussion, article preparation, selection of screening compounds), and the Russian Science Foundation, No. 17-74-30012, IBG, USC, RAS (HTS).

References

  1. 1.
    T. Fowler, D. Walker, and S. Davies, Ann. N. Y. Acad. Sci., 1323, 1 – 10 (2014).CrossRefGoogle Scholar
  2. 2.
    D. Andersson and D. Hughes, Nat. Rev. Microbiol., 12, 465 – 478 (2014).CrossRefGoogle Scholar
  3. 3.
    WHO. Antimicrobial resistance: Global report on surveillance 2014. (2014); Available from: http: // www.who.int / drugresistance / documents / AMR_report_Web_slide_set.pdf?ua=1Google Scholar
  4. 4.
    WHO publishes list of bacteria for which new antibiotics are urgently needed 2017; Available from: http: // www.who.int / mediacentre / news / releases / 2017 / bacteria-antibiotics-needed / en /.Google Scholar
  5. 5.
    Editorial, Nat. Med., 16, 347 (2010).Google Scholar
  6. 6.
    I. Osterman, E. Komarova, D. Shiryaev, et al., Antimicrob. Agents Chemother., AAC.02117 – 16 (2016).Google Scholar
  7. 7.
    E. Komarova (Andreyanova), I. Osterman, et al., Biochimie, 133, 45 – 55 (2017).Google Scholar
  8. 8.
    P. Sergiev, I. Osterman, A. Golovina, et al., Biomed. Khim., 62(2), 117 – 123 (2016).CrossRefGoogle Scholar
  9. 9.
    G. Zurawski, D. Elseviers, G. Stauffer, and C. Yanofsky, Proc. Natl. Acad. Sci. USA, 75, 5988 – 5992 (1978).CrossRefGoogle Scholar
  10. 10.
    I. Osterman, I. Prokhorova, V. Sysoev, et al., Antimicrob. Agents Chemother., 56, 1774 – 1783 (2012).CrossRefGoogle Scholar
  11. 11.
    P. Ysern, B. Clerch, M. Castano, et al., Mutagenesis, 5(1), 63 – 66 (1990).CrossRefGoogle Scholar
  12. 12.
    ChemRar TsVT; http: // chemrar.ru / biblioteki-soedinenijdlya-hts /Google Scholar
  13. 13.
    T. Baba and H. Mori, Methods Mol. Biol. Clifton N. J., 416, 171 – 181 (2008).CrossRefGoogle Scholar
  14. 14.
    ChemiDoc TM Imaging Systems 2017; Available from: http: //www.bio-rad.com / en-us / category / chemidoc-imaging-systems.Google Scholar
  15. 15.
    Image Lab TM Software 2017; Available from: http: //www.bio-rad.com / en-us / product / image-lab-software.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ya. A. Ivanenkov
    • 1
    • 2
    • 3
  • E. S. Komarova (Andreyanova)
    • 4
  • I. A. Osterman
    • 4
  • P. V. Sergiev
    • 4
  • R. S. Yamidanov
    • 3
  • E. V. Deineka
    • 1
    Email author
  • V. A. Terent’ev
    • 3
  • G. I. Fil’kov
    • 1
  • A. A. Sofronova
    • 7
  • A. G. Mazhuga
    • 2
    • 5
    • 6
  • O. A. Dontsova
    • 4
  1. 1.Moscow Institute of Physics and Technology (State University)Moscow RegionRussia
  2. 2.Department of ChemistryM. V. Lomonosov Moscow State UniversityMoscowRussia
  3. 3.Institute of Biochemistry and Genetics, Ufa Scientific CenterRussian Academy of SciencesUfaRussia
  4. 4.A. N. Belozersky Research Institute of Physico-Chemical BiologyM. V. Lomonosov Moscow State UniversityMoscowRussia
  5. 5.National University of Science and Technology Moscow Institute of Steel and Alloys (MISiS)MoscowRussia
  6. 6.D. I. Mendeleev University of Chemical Technology of RussiaMoscowRussia
  7. 7.Department of Bioengineering and BioinformaticsM. V. Lomonosov Moscow State UniversityMoscowRussia

Personalised recommendations