Synthesis and antituberculosis activity of new 5-alkynyl derivatives of 2-thiouridine: application of new scaffold

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅存取

详细

We herein describe new potent inhibitors of mycobacteria based on 5-substituted 2-thiouridine derivatives. A series of new 5-alkynyl-substituted 2-thiouridine derivatives were synthesized via palladium-catalysed Sonogashira cross-coupling reaction of 5-iodo-2-thiopyrimidine base with terminal acetylenes with good yields in DMF at room temperature. It was found that sulfur atom in C2 position of pyrimidine ring had no impact on yields of target compounds. All obtained compounds were evaluated for their antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis at concentrations of 0.1-100 µg/ml using MABA test. Synthesized nucleosides showed high antimycobacterial activity against Mycobacterium bovis and Mycobacteri um tuberculosis. The obtained MIC50 values of 2-thionucleosides 14, 15 and 16 (0.28-0.75 µg/ml) significantly exceed characteristics of reference drug rifampicin, D-cycloserine and isoniazid, which gives prerequisites for further more detailed studies.

作者简介

Ya. Platonova

Lomonosov Moscow State University

Email: knoposk@gmail.com

V. Kirillova

Lomonosov Moscow State University

A. Volov

Lomonosov Moscow State University

S. Savilov

Lomonosov Moscow State University;Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences

参考

  1. World Health Organization. Global Tuberculosis Report. World Health Organization. Geneva, Switzerland. 2021.
  2. World Health Organization. Global Tuberculosis Report. World Health Organization. Geneva, Switzerland. 2014.
  3. Zumla A., Nahid P., Cole S.T. Nat. Rev. Drug Discov. 2013, 12, 388-404. doi: 10.1038/nrd4001
  4. Klopper M., Warren R.M., Hayes C., van Pittius N.C.G., Streicher E.M., Muller B., Sirgel F.A., Chabula-Nxiweni M., Hoosain E., Coetzee G., Trollip A.P. Emerg. Infect. Dis. 2013, 19, 449-455. doi: 10.3201/eid1903.120246
  5. Slomski A. J. Am. Med. Assoc. 2013, 309, 1097-1098. doi: 10.1001/jama.2013.1802
  6. Koul A., Arnoult E., Lounis N., Guillemont J., Andries K. Nature. 2011, 469, 483-490. doi: 10.1038/nature09657
  7. Fernandes G.F.S., Jornada D.H., Souza P.C., Man Chin C., Pavan F.R., Santos J.L. Curr. Med. Chem. 2015, 22, 3133-3161. doi: 10.2174/0929867322666150818103836
  8. Bloemberg G.V., Keller P.M., Stucki D., Trauner A., Borrell S., Latshang T., Coscolla M., Rothe T., H�mke R., Ritter C., B�ttger, E.C. N. Engl. J. Med. 2015, 373, 1986-1988. doi: 10.1056/NEJMc1505196
  9. Zhang S., Chen J., Cui P., Shi W., Shi X., Niu H., Chan D., Yew W.W., Zhang W., Zhang Y. Antimicrob. Agents Chemother. 2016, 60, 2542-2544. doi: 10.1128/AAC.02941-15
  10. Segala E., Sougakoff W., Nevejans-Chauffour A., Jarlier V., Petrella S. Antimicrob. Agents Chemother. 2012, 56, 2326-2334. doi: 10.1128/AAC.06154-11
  11. Srivastav N.C., Manning T., Kunimoto D.Y., Kumar R. Bioorg. Med. Chem. 2007, 15, 2045-2053. doi: 10.1016/j.bmc.2006.12.032
  12. Srivastav N.C., Rai D., Tse C., Agrawal B., Kunimoto D.Y., Kumar R. J. Med. Chem. 2010, 53, 6180-6187. doi: 10.1021/jm100568q
  13. Platonova Ya.B., Volov A.N., Tomilova L.G. Bioorg. Med. Chem. Lett. 2020, 30, 127351. doi: 10.1016/j.bmcl.2020.127351
  14. Shigi N. Front. Genet. 2014, 5, 1-11. doi: 10.3389/fgene.2014.00067
  15. Jackman J.E., Alfonzo J.D. Wiley Interdiscip. Rev. RNA. 2013, 4, 35-48. doi: 10.1002/wrna.1144
  16. Hilbert G.E., Johnson T.B. J. Am. Chem. Soc. 1930, 52, 4489-4494. doi: 10.1021/ja01374a045

补充文件

附件文件
动作
1. JATS XML

版权所有 © Russian Academy of Sciences, 2023