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

Antiplasmodial activity of chalcone derivatives compound through phagocytosis of kupffer cells in experimental malaria hosts

  • Lilik Wijayanti ,
  • Paramasari Dirgahayu ,
  • Yulia Sari ,
  • Danus Hermawan ,
  • Ida Nurwati ,

Abstract

Introduction: Malaria is still one of the major health problems, specifically due to drug resistance in Plasmodium, which encourages extensive research to find effective alternatives. One of the new antimalarial compounds is chalcone-derivative compound (E)-1-(4-aminophenyl)-3-(2,3-dimethoxy phenyl)prop-2-en-1-one. However, its potency is still needed to be evaluated. Therefore, this study aimed to determine the efficacy and identify the pharmacological mechanism of this chalcone-derivative. 

Methods: An experiment using post-test only with control group design was conducted from May 2016 to July 2017 in the laboratory of Parasitology and Clinical Pathology Faculty of Medicine, Universitas Gadjah Mada. Swiss mice were used and infected with Plasmodium before being divided into nine groups with different concentrations of (E)-1-(4-aminophenyl)-3-(2,3-dimethoxy phenyl)prop-2-en-1-one. Histological examination was conducted to count the number of Kupffer cells and the proportion of Kupffer cells that had phagocytosed the Plasmodium.

Results: Both doxycycline and (E)-1-(4-aminophenyl)-3-(2,3-dimethoxy phenyl)prop-2-en-1-one  decreased the parasitemia in the tested mice with higher efficacy was observed in the doxycycline group. Likewise, both compounds also increase the number of  Kupffer cells which become phagocytes of erythrocytes containing Plasmodium was higher in the treatment group than in the control group (p 0.000 <0.05). Substance (E)-1-(4-aminophenyl)-3-(2,3-dimethoxy phenyl) prop-2-en-1-one may act as an antimalarial by phagocytes of erythrocytes containing Plasmodium.

Conclusion In conclusion, the (E)-1-(4-aminophenyl)-3-(2,3-dimethoxy phenyl)prop-2-en-1-one exhibited potent antimalarial activity via the phagocytic activity of Kupffer cells. This compound may be developed into a new antimalarial drug.

References

  1. Papua DKP. Profil Kesehatan Provinsi Papua Tahun 2017. Dinas Kesehatan Provinsi Papua; 2017. https://www.kemkes.go.id/resources/download/profil/PROFIL_KES_PROVINSI_2017/34_Papua_2017.pdf
  2. Septiawan M, Budayatin B, Wiyono HT, Senjarini K. Immunogenity of Protein Extract from Salivary Gland of Anopheles aconitus in Malaria Endemic Area. J ILMU DASAR. 2017;18(1):25. doi:10.19184/jid.v18i1.2372
  3. Amato Roberto, Pharath Lim, Olivo Miotto, Chanaki Amaratunga, Dalin Dek, Richard D Pearson, Jacob Almagro-Garcia ATN, Sokunthea Sreng, Seila Suon, Eleanor Drury, Dushyanth Jyothi, Jim Stalker, Dominic P Kwiatkowski RMF. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis. 2017;17(2):164-173. doi:10.1016/S1473-3099(16)30409-1.Genetic
  4. Guantai EM, Ncokazi K, Egan TJ, et al. Design, synthesis and in vitro antimalarial evaluation of triazole-linked chalcone and dienone hybrid compounds. Bioorganic Med Chem. 2010;18(23):8243-8256. doi:10.1016/j.bmc.2010.10.009
  5. Pingaew R, Saekee A, Mandi P, et al. Synthesis, biological evaluation and molecular docking of novel chalcone-coumarin hybrids as anticancer and antimalarial agents. Eur J Med Chem. 2014;85:65-76. doi:10.1016/j.ejmech.2014.07.087
  6. Go M, Liu M, Wilairat P, Rosenthal PJ, Saliba KJ, Kirk K. Antiplasmodial Chalcones Inhibit Sorbitol-Induced Hemolysis of. 2004;48(9):3241-3245. doi:10.1128/AAC.48.9.3241
  7. Yadav N, Dixit SK, Bhattacharya A, et al. Antimalarial Activity of Newly Synthesized Chalcone Derivatives In Vitro. Chem Biol Drug Des. 2012;80(2):340-347. doi:10.1111/j.1747-0285.2012.01383.x
  8. Suwito H, Jumina, Mustofa, 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(12):21473-21488. doi:10.3390/molecules191221473
  9. Setyarini II. Antiplasmodial activity and selectivity of chalcone derivatives. Published online 2015.
  10. Wijayanti L, Purwanto B, Mudigdo A, Suwito H, Dirgahayu P. The Antiplasmodial Activity of Chalcone Derivatives Through the Inhibition of Hemozoin Formation And the Increased Number of Stomatocytes. 2018;(January):251-251. doi:10.26911/mid.icph.2018.05.13
  11. Wijayanti L, Yarso KY, Purwanto B, et al. The antiplasmodial activity of chalcone derivative through the inhibition of haemozoin formation and the induction of stomatocytes formation. Bali Med J. 2019;8(1):365. doi:10.15562/bmj.v8i1.1196
  12. Lee JS, Bukhari SNA, Mohd Fauzi N. Effects of chalcone derivatives on players of the immune system. Drug Des Devel Ther. 2015;9:4761-4778. doi:10.2147/DDDT.S86242
  13. Parlapalli A, Manda S. Pharmacophore. 2015;6(5):243-248.
  14. Hans RH, Guantai EM, Lategan C, et al. synthesis, antimalarial and antitubercular activity of acetylenic chalcones. Bioorganic Med Chem Lett. 2010;20(3):942-944. doi:10.1016/j.bmcl.2009.12.062
  15. Tadigoppula N, Korthikunta V, Gupta S, et al. synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents. J Med Chem. 2013;56(1):31-45. doi:10.1021/jm300588j
  16. Park P-H, Kim HS, Jin XY, et al. KB-34, a newly synthesized chalcone derivative, inhibits lipopolysaccharide-stimulated nitric oxide production in RAW 264.7 macrophages via heme oxygenase-1 induction and blockade of activator protein-1. Eur J Pharmacol. 2009;606(1):215-224. doi:https://doi.org/10.1016/j.ejphar.2008.12.034
  17. Park SH, Kwak JA, Jung SH, et al. Piperidylmethyloxychalcone improves immune-mediated acute liver failure via inhibiting TAK1 activity. Exp Mol Med. 2017;49(11):1-10. doi:10.1038/emm.2017.156
  18. Frölich S, Schubert C, Bienzle U, Jenett-Siems K. In vitro antiplasmodial activity of prenylated chalcone derivatives of hops (Humulus lupulus) and their interaction with haemin. J Antimicrob Chemother. 2005;55(6):883-887. doi:10.1093/jac/dki099
  19. Mi-Ichi F, Miyadera H, Kobayashi T, et al. Parasite mitochondria as a target of chemotherapy: Inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain. Ann N Y Acad Sci. 2005;1056:46-54. doi:10.1196/annals.1352.037
  20. Chu J, Guo CL. Design and Discovery of Some Novel Chalcones as Antioxidant and Anti-Inflammatory Agents via Attenuating NF-κB. Arch Pharm (Weinheim). 2016;349(1):63-70. doi:10.1002/ardp.201500349
  21. Sarda SR, Jadhav WN, Bhusare SR, et al. Solvent-free NaOH-Al 2 O 3 supported synthesis of Ar. 2009;1(2):265-269.
  22. Singh H, Sidhu S, Chopra K, Khan MU. Hepatoprotective effect of trans-Chalcone on experimentally induced hepatic injury in rats: Inhibition of hepatic inflammation and fibrosis. Can J Physiol Pharmacol. 2015;94(8):879-887. doi:10.1139/cjpp-2016-0071

How to Cite

Wijayanti, L., Dirgahayu, P., Sari, Y., Hermawan, D., & Nurwati, I. (2020). Antiplasmodial activity of chalcone derivatives compound through phagocytosis of kupffer cells in experimental malaria hosts. Bali Medical Journal, 9(3), 912–917. https://doi.org/10.15562/bmj.v9i3.2021

HTML
0

Total
14

Share

Search Panel