Parasites, Hosts and Diseases

"antimalarial drug"

Original Articles

In Vitro Evaluation of Two Novel Antimalarial Derivatives of SKM13: SKM13-MeO and SKM13-F: Thuy-Tien Thi Trinh, Young-ah Kim, Hyelee Hong, Linh Thi Thuy Le, Hayoung Jang, Soon-Ai Kim, Hyun Park, Hak Sung Kim, Seon-Ju Yeo; Korean J Parasitol 2022;60(6):401-407.
Published online December 22, 2022; DOI: https://doi.org/10.3347/kjp.2022.60.6.401

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.

Citations

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Design, Synthesis and in vitro Evaluation of Primaquine and Diaminoquinazoline Hybrid Molecules Against the Malaria Parasite
Mukul Kore, Anjani G. Rao, Dimple Acharya, Shrikant S. Kirwale, Amritansh Bhanot, Abhishek Govekar, Ajeet Kumar Mohanty, Aniruddha Roy, Shruthi S. Vembar, Sandeep Sundriyal
Chemistry – An Asian Journal.2025;[Epub] CrossRef
Evaluation of the antimalarial activity of SAM13-2HCl with morpholine amide (SKM13 derivative) against antimalarial drug-resistant Plasmodium falciparum and Plasmodium berghei infected ICR mice
Hyelee Hong, Kwonmo Moon, Thuy-Tien Thi Trinh, Tae-Hui Eom, Hyun Park, Hak Sung Kim, Seon-Ju Yeo
Parasites, Hosts and Diseases.2024; 62(1): 42. CrossRef

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Aspartic proteases of Plasmodium vivax are highly conserved in wild isolates: Byoung-Kuk Na, Eung-Goo Lee, Hyeong-Woo Lee, Shin-Hyeong Cho, Young-An Bae, Yoon Kong, Jong-Koo Lee, Tong-Soo Kim; Korean J Parasitol 2004;42(2):61-66.
Published online June 20, 2004; DOI: https://doi.org/10.3347/kjp.2004.42.2.61

Abstract
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The plasmepsins are the aspartic proteases of malaria parasites. Treatment of aspartic protease inhibitor inhibits hemoglobin hydrolysis and blocks the parasite development in vitro suggesting that these proteases might be exploited their potentials as antimalarial drug targets. In this study, we determined the genetic variations of the aspartic proteases of Plasmodium vivax (PvPMs) of wild isolates. Two plasmepsins (PvPM4 and PvPM5) were cloned and sequenced from 20 P. vivax Korean isolates and two imported isolates. The sequences of the enzymes were highly conserved except a small number of amino acid substitutions did not modify key residues for the function or the structure of the enzymes. The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics.

Citations

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Arun Sharma, Alex Eapen, Sarala K. Subbarao
The Journal of Biochemistry.2005; 138(1): 71. CrossRef