Skip to main content Skip to main navigation menu Skip to site footer

The antiplasmodial activity of chalcone derivative through the inhibition of haemozoin formation and the induction of stomatocytes formation

  • Lilik Wijayanti ,
  • Kristanto Yuli Yarso ,
  • Bambang Purwanto ,
  • Ambar Mudigdo ,
  • Hery Suwito ,
  • Paramasari Dirgahayu ,
  • Mustofa Mustofa ,


Abstract

Background. One of methoxy aminochalcone derivatives, (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one has been synthesized and proven it's in vitro antiplasmodial activity. In this study, we reported in vivo antiplasmodial activity of this compound against Plasmodium berghei infected mice. Its effect on the haemozoin and erythrocytes stomatocytes formations was also evaluated.

Methods. The in vivo antiplasmodial activity was evaluated on P. berghei infected mice by the classical 4-day suppressive test. The effect of the tested compound on the haemozoin formation inhibition was evaluated by flowcytometry, whereas its effect on the stomatocytes formation was evaluated by microscopic examination of the thin blood smear. Doxucycline was used as positive control. The median effective dose (ED50), which is the dose leading to 50% parasite growth inhibition or haemozoin formation inhibition or stomatocytes formation of tested compound and doxycycline were determined using probit analysis and compared using t test.

Results: The ED50 of tested compound to parasite growth inhibition were 17.36 ± 4.59 mg/kg BW. Furthermore, this compound exhibited on inhibition of haemozoin formation with the ED50 of 18.56±5.19 mg/kg BW and induction of stomatoytes formation with the ED50 more than > 160 mg/kg BW.

Conclusion: The (E)-1-(4-aminophenyl)-3-(2,3-dimethoxyphenyl)prop-2-en-1-one exhibits potent antimalarial activity via inhibition of haemozoin formation and induction of stomatocytes formation. This compound might be developed into a new antimalarial drug.

Keywords: antiplasmodial chalcone Plasmodium haemozoin

References

  1. Carter KH, Escalada RP, Sing P. Malaria. In: Marcondes CB editor. Arthropod borne diseases. New York : Springer Publishing Company, 2016: 325 – 346. http://dx.doi.org/10.1007/978-3-319-13884-8
  2. World Health Organization. World malaria report 2017. Geneva: World Health Organization, 207. Licence: CC BY-NC-SA 3.0 IGO
  3. Kementerian Kesehatan Republik Indonesia. Epidemiologi malaria di Indonesia. Buletin Jendela Data dan Informasi Kesehatan, 2016:186 – 188
  4. Mutabingwa TK. Artemisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy! Acta Trop, 2005;95(3):305-315. http://dx.doi.org/10.1016/j.actatropica.2005.06.009
  5. Thu AM, Phyo AP, Landier J, Parker DM, Nosten FH. Combating multidrug-resistant Plasmodium falciparum malaria. FEBS J 2017; 2569-2578. http://dx.doi.org/10.1111/febs.14127.
  6. Lu F, Culleton R, Zang M, Ramaprasad A, Seidlein L, Zhou H, et al. Emergence of indigenous artimisinin resistant Plasmodium falciparum in Africa. N Engl J Med 2017; 376:991-993. http://dx.doi.org/10.1056/NEJMc1612765
  7. WHO. April 2017. Status report on artemisinin and ACT resistance. Available from: http://www.who.int/malaria/publications/atoz/artemisinin-resistance-april2017/en/
  8. Chavan BB, Gadekar AS, Mehta PP, Vawhal PK, Kolsure AK, Chabukswar AR. Synthesis and medical significance of chalcone: a review. Asian J Biomed Pharm Sci 2015; 6(56):1-7.
  9. Ram VJ, Saxena A, Srivastana S, Chandra S. Oxygenated chalcones and bischalcones as potential antimalarial agents. Bioorg Med Chem Lett 2000; 10:2159-2161.
  10. Suwito H, Jumina, Mustofa, Pudjiastuti P, Fanani MZ, Kimata-Ariga Y, et al. Design and synthesis of chalcone derivatives as inhibitors of the ferredoxin – ferredoxin – NADP+ reductase interaction of Plasmodium falciparum: pursuing new antimalarial agents. Molecules 2014; (19): 21473-21488. http://dx.doi.org/10.3390/ molecules191221473
  11. Setyarini II. Antiplasmodial activity and selectivity of chalcone derivatives. [Thesis]. Postgraduate Program of Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, 2015.
  12. Frita R, Rebelo M, Pamplona A, Figario AM, Mota MM, Grobusch MP, et al. Simple flowcytometric detection of haemozoin containing leukocytes and erythrocytes for research on diagnosis, immunology and drug sensitivity testing. Malar J 2011; 10(74): 1-14. http://dx.doi.org/10.1186/1475-2875-10-74.
  13. Fong KY & Wright DW. Haemozoin and antimalarial drugs discovery. Future Med Chem 2013; 5(12): 1437-1450. http://dx.doi.org/10.4155/fmc.13.113.
  14. Ziegler HL, Franzyk H, Sairafianpour M, Tabatabai M, Tehrani MD, Bagherzadeh K, et al. Erythrocyte membrane modifying agents and the inhibition of Plasmodium falciparum growth: structure-activity relationships for betulinic acid analogues. Bioorg Med Chem 2004; 12:119-127. http://dx.doi.org/10.1016/j.bmc.2003.10.010
  15. Ziegler HL, Staerk D, Christensen J, Hviid L, Hagerstrand H, Jaroszewski JW. In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasitic growth by incorporation of stomatocytogenic amphiphiles into erythrocytes membrane. Antimicrob Agents Chemother 2002; 46(5): 1441-1446. http://dx.doi.org./10.1128/AAC.46.5.1441-1446.2002
  16. Rojas-Aguirre Y, Hernandez-Luis F, Mendoza-Martinez C, Sotomayor CP, Aguilar LF, Villena F, et al. Effects of an antimalarial quinazoline derivative on human erythrocytes and on cell membrane molecular models. Biochim Biophys Acta 2012; 1818(3):738-746. http://dx.doi.org/10.1016/j.bbamem.2011.11.026
  17. Peters W, Portus JH, Robinson BL. The chemotheraphy of rodent malaria XXII. The value of drug-resistant strains of Plasmodium berghei in screening for blood schizontocidal activity. Ann Trop Med Parasitol 69: 155-171.
  18. Xiang W. Investigations on the antiplasmodial activity of ferrocenyl chalcones. [Dissertation], Singapore: National University of Singapore, 2005.
  19. Chen M, Chritensen SB, Zhai L, Rasmussen MH, Theander TG, Frokjaer S, et al. The novel oxygenated chalcone, 2,4-dimethoxy-4’-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo. J Infect Dis 1997; 176(5): 1327-1333.
  20. Domínguez JN, León C, Rodrigues J, de Domígues NG, Gut J, Rosenthal PJ. Synthesis and evaluation of new antimalarial phenylurenyl chalcone erivatives. J Med Chem 2005; 48:3654-3658.
  21. Coronado LM, Nadovich CT, Spadafora C. Malaria hemozoin: from target to tool. Biochim Biphys Acta 2014; 1840(6): 2032-2041.
  22. Fong KY & Wright DW. Hemozoin nd antimalarial drug discovery. Future Med Chem 2013; 5(12): 1437-1450.
  23. Sinha S, Medhi B and Sehgal R. Chalcone as an emerging lead molecule for antimalarial therapy: a review. J Modern Med Chem 2013; 1: 64-77.
  24. Cooke BM, Mohandas N, Coppel RL. The malaria-infected red blood cell: structural and functional changes. Adv Parasitol 2001; 50: 1-86.
  25. Desai AS, Bezrukov SM, Zimmerberg J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 2000; 406: 1001-1005.
  26. Ziegler HL, Staerk D, Christensen J, Hviid L, Hägerstrand H, Jaroszewski J. In vitro Plasmodium falciparum drug sensitivity assay: inhibition of parasite growth by incorporation of stomatocytogenic amphiphiles into the erythrocyte membrane. Antimicrob Agent Chemother 2002; 1441-1446.
  27. Ziegler HL, Hansen HS, Staerk D, Christensen SB, Hägerstrand H, Jaroszewski JW. The antiparasitic compound licochalcone A is a potent echinocytogenic agent that modifies the erythrocyte membrane in the concentration range where antiplasmodial activity is observed. Antimicrob Agents Chemother 2004; 48: 4067 – 4071

How to Cite

Wijayanti, L., Yarso, K. Y., Purwanto, B., Mudigdo, A., Suwito, H., Dirgahayu, P., & Mustofa, M. (2019). The antiplasmodial activity of chalcone derivative through the inhibition of haemozoin formation and the induction of stomatocytes formation. Bali Medical Journal, 8(1), 365–370. https://doi.org/10.15562/bmj.v8i1.1196
ACM ACS APA ABNT Chicago Harvard IEEE MLA Turabian Vancouver
Download Citation
Endnote/Zotero/Mendeley (RIS) BibTeX

HTML
2

Total
5

Share

Search Panel

Lilik Wijayanti
Google Scholar
Pubmed
BMJ Journal

Kristanto Yuli Yarso
Google Scholar
Pubmed
BMJ Journal

Bambang Purwanto
Google Scholar
Pubmed
BMJ Journal

Ambar Mudigdo
Google Scholar
Pubmed
BMJ Journal

Hery Suwito
Google Scholar
Pubmed
BMJ Journal

Paramasari Dirgahayu
Google Scholar
Pubmed
BMJ Journal

Mustofa Mustofa
Google Scholar
Pubmed
BMJ Journal