Microbiology Independent Research Journal (MIR Journal)

Advanced search

Synthesis and study of the antimicrobial activity of nifuroxazide derivatives


The number of infections caused by microorganisms that are resistant to antibiotics and synthetic antibacterial drugs is growing fast worldwide. This is one of the most important and urgent problems in health care. The main efforts of researchers around the world are focused on solving this issue. Nitrofurans represent one of the most effective classes of antibacterial drugs. We have synthesized 4 analogues of nifuroxazide – a well known nitrofuran antibiotic – and confirmed their structures by NMR, IR spectroscopy, and mass-spectrometry. All of the obtained compounds were studied for antimicrobial and antifungal activity.
Activity against Escherichia coli, Staphylococcus aureus, Staphylococcus haemolyticus, and Pseudomonas aeruginosa was evaluated by the agar diffusion method. The synthesized compounds suppressed the growth of all the studied bacterial strains except Escherichia coli; the diameter of the inhibition zones ranged from 13.5 to 28 mm depending on the concentration of the tested compound and bacterial strain. One of the compounds studied in this project – the pyridine analogue of nifuroxazide – exceeded the activity of the standard (nifuroxazide) against the Staphylococcus aureus. The inhibitory activity of the synthesized compounds against the Candida albicans and Cryptococcus neoformans yeasts was determined using the microdilution method. The results were assessed according to the indicator color change. None of the studied compounds showed activity against these cultures.
The obtained results confirm that substituted nifuroxazides have significant antimicrobial activity and, therefore, can be considered as promising candidates for developing new antibacterial drugs.

About the Authors

N. G. Sidorov
Sechenov First Moscow State Medical University; Mechnikov Research Institute for Vaccines and Sera
Russian Federation

Nikita Sidorov


A. D. Kravchenko
Sechenov First Moscow State Medical University
Russian Federation

A. V. Poddubikov
Mechnikov Research Institute for Vaccines and Sera
Russian Federation

V. G. Arzumanian
Mechnikov Research Institute for Vaccines and Sera
Russian Federation


1. Покудина ИО, Шкурат МА, Батталов ДВ. Резистентность микроорганизмов к антимикробным препаратам. Живые и биокосные системы 2014; 10.

2. World Health Organization. Antimicrobial resistance. Available:

3. Зубов ПВ, Новикова ВВ. Разработка новых антибактериальных препаратов: проблемы и перспективы. Современные проблемы науки и образования 2015; 5.

4. Rollas S, Kucukguzel SG. Biological activities of hydrazone derivatives. Molecules 2007; 12(8), 1910-39. PubMed PMID: 17960096.

5. Thota S, Rodrigues DA, Pinheiro PSM, Lima LM, Fraga CAM, Barreiro EJ. N-Acylhydrazones as drugs. Bioorg Med Chem Lett 2018; 28(17), 2797-806. doi: 10.1016/j.bmcl.2018.07.015.

6. Tavares LC, Penna TC, Amaral AT. Synthesis and biological activity of nifuroxazide and analogs. Boll Chim Farm 1997; 136(3), 244-9. PubMed PMID: 9164164.

7. Masunari A, Tavares LC. A new class of nifuroxazide analogues: synthesis of 5-nitrothiophene derivatives with antimicrobial activity against multidrugresistant Staphylococcus aureus. Bioorg Med Chem 2007; 15(12), 4229-36. doi: 10.1016/j.bmc.2007.03.068.

8. Paula FR, Jorge SD, de Almeida LV, Pasqualoto KF, Tavares LC. Molecular modeling studies and in vitro bioactivity evaluation of a set of novel 5-nitroheterocyclic derivatives as anti-T. cruzi agents. Bioorg Med Chem 2009; 17(7), 2673-9. doi: 10.1016/j.bmc.2009.02.056.

9. Palace-Berl F, Pasqualoto KF, Jorge SD, Zingales B, Zorzi RR, Silva MN, et al. Designing and exploring active N’-[(5-nitrofuran-2-yl) methylene] substituted hydrazides against three Trypanosoma cruzi strains more prevalent in Chagas disease patients. Eur J Med Chem 2015; 96, 330-9. doi: 10.1016/j.ejmech.2015.03.066.

10. Rando DG, Avery MA, Tekwani BL, Khan SI, Ferreira EI. Antileishmanial activity screening of 5-nitro- 2-heterocyclic benzylidene hydrazides. Bioorg Med Chem 2008; 16(14), 6724-31. doi: 10.1016/j.bmc.2008.05.076.

11. Практическое руководство по антиинфекционной химиотерапии. Под ред. Л.С. Страчунского, Ю.Б. Белоусова, С.Н. Козлова. Смоленск: НИИАХ СГМА; 2007.

12. Козлов РС, Голуб АВ. Выбор антимикробных препаратов при неосложненных инфекциях мочевых путей: как принять соломоново решение? Клиническая микробиология и антимикробная химиотерапия 2014; 16(1), 18-25.

13. Drugbank. Available:

14. Sarvi S, Crispin R, Lu Y, Zeng L, Hurley TD, Houston DR, et al. ALDH1 Bio-activates Nifuroxazide to Eradicate ALDH(High) Melanoma-Initiating Cells. Cell Chem Biol 2018; 25(12), 1456-69. e6. doi: 10.1016/j.chembiol.2018.09.005.

15. Nelson MI, Viboud C, Simonsen L, Bennett RT, Griesemer SB, George KS, et al. Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918. PLoS Pathog 2008; 4(2), e1000012. doi: 10.1371/journal.ppat.1000012.

16. Yang F, Hu M, Lei Q, Xia Y, Zhu Y, Song X, et al. Nifuroxazide induces apoptosis and impairs pulmonary metastasis in breast cancer model. Cell Death Dis 2015; 6, e1701. doi: 10.1038/cddis.2015.63.

17. Zhu Y, Ye T, Yu X, Lei Q, Yang F, Xia Y, et al. Nifuroxazide exerts potent anti-tumor and antimetastasis activity in melanoma. Sci Rep 2016; 6, 20253. doi: 10.1038/srep20253.

18. World Health Organization. Prevention of hospitalacquired infections. Available:

19. Государственная фармакопея Российской Федерации XIII издание. ОФС. Определение антимикробной активности антибиотиков методом диффузии в агар.

20. Andrews JM, Testing BWPoS. BSAC standardized disc susceptibility testing method (version 8). J Antimicrob Chemother 2009; 64(3), 454-89. doi: 10.1093/jac/dkp244.

21. Определение чувствительности микроорганизмов к антимикробным препаратам. Клинические рекомендации. Межрегиональная ассоциация по клинической микробиологии и антимикробной химиотерапии; 2018, 11-18.

22. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. CLSI document M27-A. Clinical and Laboratory Standards Institute; 1997.

23. Alastruey-Izquierdo A, Melhem MS, Bonfietti LX, Rodriguez-Tudela JL. Susceptibility Test for Fungi: Clinical and Laboratorial Correlations in Medical Mycology. Rev Inst Med Trop Sao Paulo 2015; 57(Suppl 19), 57-64. doi: 10.1590/S0036-46652015000700011.

24. Rakant A, Arzumanian VG, Popkov VA. In-vitro determination of antimycotic activity of the fluconazole generics on Russian pharmaceutical market. Clin Exp Pharmacol 2017; 7(6) (Suppl), 51. doi: 10.4172/2161-1459-C1-025.

25. Yarrow D. Methods for the isolation, maintenance and identification of yeasts. Chapter 11 in C. P. Kurtzman, J. W. Fell (Eds.), The Yeasts, a Taxonomic Study, 4th ed., Elsevier, Amsterdam; 1998, pp. 77–101. doi: 10.1016/B978-044481312-1/50014-9.

26. Rando DG, Sato DN, Siqueira L, Malvezzi A, Leite CQ, do Amaral AT, et al. Potential tuberculostatic agents. Topliss application on benzoic acid [(5-nitrothiophen-2-yl)-methylene]-hydrazide series. Bioorg Med Chem 2002; 10(3), 557-60. PubMed PMID: 11814842.

27. Popiolek L, Biernasiuk A. Synthesis and investigation of antimicrobial activities of nitrofurazone analogues containing hydrazide-hydrazone moiety. Saudi Pharm J 2017; 25(7), 1097-102. doi: 10.1016/j.jsps.2017.05.006.

28. Zorzi RR, Jorge SD, Palace-Berl F, Pasqualoto KF, Bortolozzo Lde S, de Castro Siqueira AM, et al. Exploring 5-nitrofuran derivatives against nosocomial pathogens: synthesis, antimicrobial activity and chemometric analysis. Bioorg Med Chem 2014; 22(10), 2844-54. doi: 10.1016/j.bmc.2014.03.044.

29. Paula FR, Trossini GHG, Ferreira EI, Serrano SHP, Menezes CMS, and Tavares LC. Theoretical and Voltammetric Studies of 5-Nitro-heterocyclic Derivatives with Potential Trypanocidal Activities. J Braz Chem Soc 2010; 21(4), 740-9. doi: 10.1590/S0103-50532010000400022.

30. Tavares LC, Chiste JJ, Santos MG, Penna TC. Synthesis and biological activity of nifuroxazide and analogs. II. Boll Chim Farm 1999; 138(8), 432-6. PubMed PMID: 10622109.

31. Alsaeedi HS, Aljaber NA, Ara I. Synthesis and investigation of antimicrobial activity of some nifuroxazide analogues. Asian J Chem 2015; 27(10), 3639-3646. doi: 10.14233/ajchem.2015.18896.


For citations:

Sidorov N.G., Kravchenko A.D., Poddubikov A.V., Arzumanian V.G. Synthesis and study of the antimicrobial activity of nifuroxazide derivatives. Microbiology Independent Research Journal (MIR Journal). 2019;6(1):1-9. (In Russ.)

Views: 265

ISSN 2500-2236 (Online)