Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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In Vitro Evaluation of Two Novel Antimalarial Derivatives of SKM13: SKM13-MeO and SKM13-F

  • Thuy-Tien Thi, Trinh (Department of Tropical Medicine and Parasitology, Medical Research Center, Institute of Endemic Diseases, Seoul National University) ;
  • Young-ah, Kim (College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University) ;
  • Hyelee, Hong (Department of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University) ;
  • Linh Thi Thuy, Le (Department of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University) ;
  • Hayoung, Jang (Department of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University) ;
  • Soon-Ai, Kim (College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University) ;
  • Hyun, Park (Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University) ;
  • Hak Sung, Kim (College of Pharmacy, Institute of Pharmaceutical Research and Development, Wonkwang University) ;
  • Seon-Ju, Yeo (Department of Tropical Medicine and Parasitology, Medical Research Center, Institute of Endemic Diseases, Seoul National University)
  • Received : 2022.07.10
  • Accepted : 2022.11.28
  • Published : 2022.12.31
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Abstract

Antimalarial drugs play an important role in the control and treatment of malaria, a deadly disease caused by the protozoan parasite Plasmodium spp. The development of novel antimalarial agents effective against drug-resistant malarial parasites is urgently needed. The novel derivatives, SKM13-MeO and SKM13-F, were designed based on an SKM13 template by replacing the phenyl group with electron-donating (-OMe) or electron-withdrawing groups (-F), respectively, to reverse the electron density. A colorimetric assay was used to quantify cytotoxicity, and in vitro inhibition assays were performed on 3 different blood stages (ring, trophozoite, and schizonts) of P. falciparum 3D7 and the ring/mixed stage of D6 strain after synchronization. The in vitro cytotoxicity analysis showed that 2 new SKM13 derivatives reduced the cytotoxicity of the SKM13 template. SKM13 maintained the IC50 at the ring and trophozoite stages but not at the schizont stage. The IC50 values for both the trophozoite stage of P. falciparum 3D7 and ring/mixed stages of D6 demonstrated that 2 SKM13 derivatives had decreased antimalarial efficacy, particularly for the SKM13-F derivative. SKM13 may be comparably effective in ring and trophozoite, and electron-donating groups (-OMe) may be better maintain the antimalarial activity than electron-withdrawing groups (-F) in SKM13 modification.

Keywords

Acknowledgement

Plasmodium falciparum D6 (ATCC MRA-285) was obtained from BEI Resources, NIAID, NIH: Plasmodium falciparum, Strain D6, MRA-285, contributed by Dennis E. Kyle. Plasmodium falciparum 3D7 was obtained from BEI Resources, NIAID, NIH: Plasmodium falciparum, Strain 3D7 (GL Clone), MRA-1001, contributed by Megan G. Dowler. This work was supported by the New Faculty Startup Fund of Seoul National University (800-20200549).

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