Antimicrobial activity investigation of natural bromotyrosine derivatives

  • H. Ehrlich
  • V.P. Kovalchuk
  • A.S. Voronkina
  • I.M. Vovk
  • І.Yu. Sidko
  • M.S. Tretyakov
Keywords: bromotyrosines, antimicrobial activity, gram-positive bacteria.


Annotation. The relevance of the search for new natural antimicrobials is dictated by global spread of antimicrobial resistance. Studies of marine sponges of the class Demospongiae, including more than 7300 species, have become promising from the pharmacological point of view. Sponges produce a wide range of biologically active substances of different classes such as steroids, isoprene, alkaloids, terpenoids, etc., which can inhibit the growth of pathogenic microorganisms or kill them. The trial of brominated isoxazoline alkaloid derivates named bromotyrosines has been enough promising. The aim of our work was to determine the antimicrobial activity of aeroplysinin-1 against clinical antibiotic-resistant strains of gram-positive bacteria and fungi of the genus Candida. The aeroplysinin-1 substance was isolated by methanol extraction from desiccated specimens of sponge Aplysina aerophoba followed with its separation by column chromatography in the Extreme Biomimetics Laboratory of the Electronics and Sensor Materials Institute, Freiberg Mining Academy, UT (Germany). Well method was used to determine antimicrobial action of the tested substance against clinical strains of bacteria and fungi (S. aureus, C. acnes, C. albicans). Aeroplysinin-1 was found to demonstrate high antibacterial activity against clinical strains of the genera Cutibacterium, Staphylococcus. The inhibiting growth zones around the wells filled with 0.1% solution of aeroplysinin-1 in dimethyl sulfoxide had diameters of 35.4±3.2 mm, 32.1±2.8 mm and 26.5±2.5 mm for cutibacterium, enterococci, and staphylococci, respectively. It was revealed aeroplysinin-1 had no activity against fungi of the genus Candida. So, after a comprehensive study of pharmacological properties of this natural bromotyrosine compound, which is a secondary metabolite of marine sponges Aplysina aerophoba, it can be added to the list of alternative compounds to struggle multiresistent to modern antibiotics pathogens causing human diseases.


1. Volianskyi, Yu. L., Hrytsenko, I. S., & Shyrobokov, V. P. (2004). Vyvchennia spetsyfichnoi aktyvnosti protymikrobnykh likarskykh zasobiv: metodychni rekomendatsii [Specific activity detection of antimicrobial medicines: Guidelines]. Kyiv: Zdorovia.

2. Vyznachennia chutlyvosti mikroorhanizmiv do antybakterialnykh preparativ. Metodychni vkazivky. MV 9.9.5-143. - 2007. [Detection of microbial susceptibility to antimicrobials. Guidelines. MV 9.9.5-143. - 2007]. Kyiv: MOZ Ukrainy. Vziato z

3. Andersen, R. J., & Faulkner, D. J. (1975). Synthesis of aeroplysinin-1 and related compounds. Jornal of the American Chemical Society, 97, 936–937.

4. Bechmann, N., Ehrlich, H., Eisenhofer, G., Ehrlich, A., Meschke, S., Ziegler, C., & Bornstein, S. (2018). Anti-Tumorigenic and Anti-Metastatic Activity of the Sponge-Derived Marine Drugs Aeroplysinin-1 and Isofistularin-3 against Pheochromocytoma In Vitro. Marine Drugs, 16 (5), 172. doi: 10.3390/md16050172.

5. Binnewerg, B., Schubert, M.,Voronkina, A. & Ehrlich, H. (2020). Marine biomaterials: Biomimetic and pharmacological potential of cultivated Aplysina aerophoba marine demosponge. Material Science and Engineering: C, 109, 110566.

6. Datta, D., Nath Talapatra, S., & Swarnakar, S. (2015). Bioactive compounds from marine invertebrates for potential medicines — An overview. International Letters of Natural Science, 7, 42–61. DOI: 10.18052/

7. Ebel, R., Elbrächter, M., Kirchner, M., & Proksch, P. (1996). Defense metabolites from the marine sponge Verongia aerophoba. Biochemical Systematics and Ecology, 24, 1–12.

8. Ebel, R., Brenzinger, M., Kunze, A., Gross, H. J., & Proksch, P. (1997). Wound activation of protoxins in marine sponge Aplysina aerophoba. Jornal of Chemical Ecology, 23, 1451–1462.

9. Ehrlich, H. (2015). Biological Materials of Marine Origin: Vertebrates, Biologically-Inspired Systems (Vol. 4). Springer. Retrieved from

10. Ehrlich, H. (2016). Extreme biomimetics. Springer. Retrieved from

11. Ehrlich, H. (2019). Marine Biological Materials of Invertebrate Origin; Biologically-Inspired Systems (Vol. 13). Springer International Publishing: Cham. Retrieved from

12. Fattorusso, E., & Minale, L. S. G. (1972). Aeroplysinin-1, an antibacterial bromo-compound from the sponge Verongia aerophoba. Jornal of Chemical Society, 1, 16–18.

13. Friedrich, A., Fisher, I., Proksch, P., Hasker, J., & Hentschel, U. (2001). Temporal variation of the microbial community associated with the mediterranean sponge Aplysina aerophoba. FEMS Microbiology Ecology,38, 105–113.

14. García-Vilas, J. A., Martínez-Poveda, B., Quesada, A. R., & Medina, M. Á. (2015). Aeroplysinin-1, a Sponge-Derived Multi-Targeted Bioactive Marine Drug. Marine Drugs, 14, 1. doi: 10.3390/md14010001.

15. Gómez-Archila, L., Zapata, W., Galeano, E., Martínez, A., Díaz, F.J., Rugeles, M.T. (2014). Bromotyrosine derivatives from marine sponges inhibit the HIV-1 replication in vitro. VITAE. Revista de la Facultad de Química Farmaceutica, 21 (2), 114–125.

16. Green, G. (1977). Ecology of toxicity in marine sponges. Marine Biology, 40, 207–215.

17. Laport, M. S., Santos, O. C. S., & Muricy, G. (2009). Marine sponges: Potential sources of new antimicrobial drugs. Current Pharmaceutical Biotechnology, 10 (1), 86–105. doi: 10.2174/138920109787048625.

18. Martínez-Poveda, B., García-Vilas, J. A., Cárdenas, C., Melgarejo, E., Quesada, A. R., & Medina, M. A. (2013). The brominated compound aeroplysinin-1 inhibits proliferation and the expression of key pro-inflammatory molecules in human endothelial and monocyte cells. PLOS ONE, 8 (1), e55203. doi: 10.1371/journal.pone.0055203.

19. Martínez-Poveda, B., Rodríguez-Nieto, S., García-Caballero, M., Medina, M. A., & Quesada, A. R. (2012). The antiangiogenic compound aeroplysinin-1 induces apoptosis in endothelial cells by activating the mitochondrial pathway. Marine Drugs, 10 (9), 2033–2046. doi: 10.3390/md10092033.

20. Tacconelli, E., Carrara, E., Savoldi, A., Kattula, D., & Burkert, F. (2017). Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics World Health Organization. Retrieved from

21. Teeyapant, R., & Proksch, P. (1993). Biotransformation of brominated compounds in the marine sponge Verongia aerophoba — Evidence for an induced chemical defense? Naturwissenschaften 80, 369–370.

22. Thoms, C., Ebel, R., & Proksch, P. (2006). Activated chemical defense in Aplysina sponges revisited. Jornal of Chemical Ecology, 32 (1), 97–123. doi: 10.1007/s10886-006-9355-x.

23. Unson, M. D., Holland, N. D., & Faulkner, D. J. (1994). A brominated secondary metabolite synthesized by the cyanobacterial symbiont of a marine sponge and accumulation of the crystalline metabolite in the sponge tissue. Marine Biology, 119, 1–11.

24. Van Soest, R. W. M., Boury-Esnault, N., & Carballo, J. L. (2017). World Porifera Database. Retrieved from

25. Weiss, B., Teeyapant, R.,Woerdenbag, H. J., & Proksch, P. (1993). Antibiotic and cytotoxic activity of brominated compounds from the marine sponge Verongia aerophoba. Zeitschrift fur Naturforschung C, 48, 939–945.

26. World Health Organization. (‎2015)‎. Global action plan on antimicrobial resistance. World Health Organization. Retrieved from
How to Cite
Ehrlich, H., Kovalchuk, V., Voronkina, A., Vovk, I., SidkoІ., & Tretyakov, M. (2020). Antimicrobial activity investigation of natural bromotyrosine derivatives. Reports of Vinnytsia National Medical University, 24(1), 45-50.

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