Brief Communication | Published:

Anti-Helicobacter pylori activities of selected N-substituted cinnamamide derivatives evaluated on reference and clinical bacterial strains

The Journal of Antibioticsvolume 71pages543548 (2018) | Download Citation


In this study, thirty-five N-substituted derivatives of cinnamic acid amide (cinnamamide) were evaluated for anti-Helicobacter pylori activity using an agar disc-diffusion method. Qualitative screening was performed on a reference H. pylori strain (ATCC 43504), resulting in the identification of the three most active compounds, 8 (R,S-(2E)-3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide, minimal inhibitory concentration, MIC = 7.5 µg/mL), 23 ((2E)-3-(4-chlorophenyl)-N-(2-hydroxycyclohexyl)prop-2-enamide, MIC = 10 µg/mL), and 28 ((2E)-3-(4-chlorophenyl)-N-(4-oxocyclohexyl)prop-2-enamide, MIC = 10 µg/mL). These compounds were further tested on twelve well-characterized clinical strains, yielding MIC values that ranged from 10 to 1000 µg/mL. Preliminary safety assessments of the compounds were made using the MTT viability test for cytotoxicity and Ames test for mutagenicity, which showed them to be generally safe, although compounds 8 and 28 showed mutagenic activity at some of the tested concentrations. The results of this study showed the anti-H. pylori potential of cinnamamide derivatives.

  • Subscribe to The Journal of Antibiotics for full access:



Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.


  1. 1.

    Eusebi LH, Zagari RM, Bazzoli F. Epidemiology of Helicobacter pylori infection. Helicobacter. 2014;19:1–5.

  2. 2.

    Konturek SJ, Konturek PC, Konturek JW, Plonka M, Czesnikiewicz-Guzik M, Brzozowski T, Bielanski W. Helicobacter pylori and its involvement in gastritis and peptic ulcer formation. J Physiol Pharmacol. 2006;57:29–50.

  3. 3.

    IARC Monograph on the Evaluation of Carcinogenic Risks to Humans. Schistosomes, liver flukes and Helicobacter pylori. Lyon, France: International Agency for Research on Cancer; 1994. Vol. 61.

  4. 4.

    Malfertheiner P, Megraud F, O’Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM, European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017;66:6–30.

  5. 5.

    Giorgio F, Principi M, De Francesco V, Zullo A, Losurdo G, Di Leo A, Ierardi E. Primary clarithromycin resistance to Helicobacter pylori: Is this the main reason for triple therapy failure? World J Gastrointest Pathophysiol. 2013;4:43–6.

  6. 6.

    Karczewska E, Klesiewicz K, Skiba I, Wojtas-Bonior I, Sito E, Czajecki K, Zwolińska-Wcisło M, Budak A. Variability in prevalence of Helicobacter pylori Strains Resistant to Clarithromycin and Levofloxacin in Southern Poland. Gastroenterol Res Pract. 2012;2012:418010.

  7. 7.

    Sugano K, Tack J, Kuipers EJ, Graham DY, El-Omar EM, Miura S, Haruma K, Asaka M, Uemura N, Malfertheiner P, Faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015;64:1353–67.

  8. 8.

    Guzman JD. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity. Molecules. 2014;19:19292–349.

  9. 9.

    Bae EA, Han MJ, Kim NJ, Kim DH. Anti-Helicobacter pylori activity of herbal medicines. Biol Pharm Bull. 1998;21:990–2.

  10. 10.

    Gunia-Krzyżak A, Żesławska E, Słoczyńska K, Koczurkiewicz P, Nitek W, Żelaszczyk D, Szkaradek N, Waszkielewicz AM, Pękala E, Marona H. Anticonvulsant activity, crystal structures, and preliminary safety evaluation of N-trans-cinnamoyl derivatives of selected (un)modified aminoalkanols. Eur J Med Chem. 2016;107:26–37.

  11. 11.

    Gunia-Krzyżak A, Żelaszczyk D, Rapacz A, Żesławska E, Waszkielewicz AM, Pańczyk K, Słoczyńska K, Pękala E, Nitek W, Filipek B, Marona H. Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3. Bioorg Med Chem. 2017;25:471–82.

  12. 12.

    Gunia A, Waszkielewicz AM, Cegła M, Marona H. Preliminary evaluation of anticonvulsant activity of some aminoalkanol and amino acid cinnamic acid derivatives. Lett Drug Des Discov. 2012;9:37–43.

  13. 13.

    Gunia-Krzyżak A, Żesławska E, Bareyre FM, Nitek W, Waszkielewicz AM, Marona H. Physicochemical and biological evaluation of a cinnamamide derivative R,S-(2E)-1-(3-hydroxypiperidin-1-yl)-3-phenylprop-2-en-1-one (KM-608) for nervous system disorders. Chem Biol Drug Des. 2017;90:244–52.

  14. 14.

    Bauer AW, Kirby WMM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966;36:493–6.

  15. 15.

    European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters; Version. 6.0 (Accessed August 13, 2017).

  16. 16.

    Kargar M, Ghorbani-Dalini S, Doosti A, Souod N. Real-time PCR for Helicobacter pylori quantification and detection of clarithromycin resistance in gastric tissue from patients with gastrointestinal disorders. Res Microbiol. 2012;163:109–13.

  17. 17.

    Gzyl A, Augustynowicz E, Dzierzanowska D, Rozynek E, Dura W, Celińska-Cedro D, Berg DE. Genotypes of Helicobacter pylori in Polish population. Acta Microbiol Pol. 1999;48:261–75.

  18. 18.

    Agudo S, Pérez-Pérez G, Alarcón T, López-Brea M. Rapid detection of clarithromycin resistant Helicobacter pylori strains in Spanish patients by polymerase chain reaction- restriction fragment length polymorphism. Rev Esp Quimioter. 2011;24:32–6.

  19. 19.

    Prado A, Petroianu GA, Lorke DE, Chambers JW. A trivalent approach for determining in vitro toxicology: examination of oxime K027. J Appl Toxicol. 2015;35:219–27.

  20. 20.

    Mortelmans K, Zeiger E. The Ames Salmonella/microsome mutagenicity assay. Mutat Res. 2000;455:29–60.

Download references


This work was supported by Jagiellonian University Medical College in Kraków (Grants K/DSC/004292, K/ZDS/005487, K/DSC/003549), the Polish National Science Center, decision on grant no. DEC-2013/11/B/NZ7/04834, and by a research grant funded by the Polish Government in the years 2011-2013 (NN404547640)​. Salmonella typhimurium strains TA98 and TA102 were kindly provided by Dr T Nohmi (Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan).

Author information


  1. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków, Poland

    • Karolina Klesiewicz
    • , Elżbieta Karczewska
    • , Paweł Nowak
    • , Iwona Skiba-Kurek
    •  & Alicja Budak
  2. Falck Medycyna Outpatient Clinic of Gastroenterology, Mazowiecka 4-6, Kraków, Poland

    • Edward Sito
  3. Department od Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków, Poland

    • Katarzyna Pańczyk
    • , Dorota Żelaszczyk
    • , Anna M. Waszkielewicz
    • , Henryk Marona
    •  & Agnieszka Gunia-Krzyżak
  4. Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, Kraków, Poland

    • Paulina Koczurkiewicz
    •  & Elżbieta Pękala


  1. Search for Karolina Klesiewicz in:

  2. Search for Elżbieta Karczewska in:

  3. Search for Paweł Nowak in:

  4. Search for Iwona Skiba-Kurek in:

  5. Search for Edward Sito in:

  6. Search for Katarzyna Pańczyk in:

  7. Search for Paulina Koczurkiewicz in:

  8. Search for Dorota Żelaszczyk in:

  9. Search for Elżbieta Pękala in:

  10. Search for Anna M. Waszkielewicz in:

  11. Search for Alicja Budak in:

  12. Search for Henryk Marona in:

  13. Search for Agnieszka Gunia-Krzyżak in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Agnieszka Gunia-Krzyżak.

About this article

Publication history






Rights and permissions

To obtain permission to re-use content from this article visit RightsLink.