Parasites, Hosts and Diseases

"chloroquine"

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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Molecular Markers for Sulfadoxine/Pyrimethamine and Chloroquine Resistance in Plasmodium falciparum in Thailand: Jiraporn Kuesap, Nutnicha Suphakhonchuwong, Lertluk Kalawong, Natthaya Khumchum; Korean J Parasitol 2022;60(2):109-116.
Published online April 20, 2022; DOI: https://doi.org/10.3347/kjp.2022.60.2.109

Abstract
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Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.

Citations

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Xyonane Segovia, Bhavya Srivastava, Sergio Serrato-Arroyo, Ashley Guerrero, Silvie Huijben
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Obafemi Yemisi Dorcas, Atokolo Austine
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Adebanjo J. Adegbola, Omotade A. Ijarotimi, Akaninyene E. Ubom, Bukola A. Adesoji, Olajide E. Babalola, Emma F. Hocke, Helle Hansson, Andria Mousa, Oluseye O. Bolaji, Michael Alifrangis, Cally Roper
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European Journal of Medicinal Chemistry.2023; 259: 115699. CrossRef

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Plasmodium vivax Drug Resistance Genes; Pvmdr1 and Pvcrt-o Polymorphisms in Relation to Chloroquine Sensitivity from a Malaria Endemic Area of Thailand: Kanchana Rungsihirunrat, Poonuch Muhamad, Wanna Chaijaroenkul, Jiraporn Kuesap, Kesara Na-Bangchang; Korean J Parasitol 2015;53(1):43-49.
Published online February 27, 2015; DOI: https://doi.org/10.3347/kjp.2015.53.1.43

Abstract
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The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 μl) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC₅₀ of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.

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Mini Review

Plasmodium vivax Malaria: Status in the Republic of Korea Following Reemergence: Jae-Won Park, Gyo Jun, Joon-Sup Yeom; Korean J Parasitol 2009;47(Suppl):S39.
Published online October 26, 2009; DOI: https://doi.org/10.3347/kjp.2009.47.S.S39

Abstract
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The annual incidence of Plasmodium vivax malaria that reemerged in the Republic of Korea (ROK) in 1993 increased annually, reaching 4,142 cases in 2000, decreased to 864 cases in 2004, and once again increased to reach more than 2,000 cases by 2007. Early after reemergence, more than two-thirds of the total annual cases were reported among military personnel. However, subsequently, the proportion of civilian cases increased consistently, reaching over 60% in 2006. P. vivax malaria has mainly occurred in the areas adjacent to the Demilitarized Zone, which strongly suggests that malaria situation in ROK has been directly influenced by infected mosquitoes originating from the Democratic People's Republic of Korea (DPRK). Besides the direct influence from DPRK, local transmission within ROK was also likely. P. vivax malaria in ROK exhibited a typical unstable pattern with a unimodal peak from June through September. Chemoprophylaxis with hydroxychloroquine (HCQ) and primaquine, which was expanded from approximately 16,000 soldiers in 1997 to 200,000 soldiers in 2005, contributed to the reduction in number of cases among military personnel. However, the efficacy of the mass chemoprophylaxis has been hampered by poor compliance. Since 2000, many prophylactic failure cases due to resistance to the HCQ prophylactic regimen have been reported and 2 cases of chloroquine (CQ)-resistant P. vivax were reported, representing the first-known cases of CQ-resistant P. vivax from a temperate region of Asia. Continuous surveillance and monitoring are warranted to prevent further expansion of CQ-resistant P. vivax in ROK.

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Original Article

Clinical efficacy of chloroquine versus artemether-lumefantrine for Plasmodium vivax treatment in Thailand: Srivicha Krudsood, Noppadon Tangpukdee, Sant Muangnoicharoen, Vipa Thanachartwet, Nutthanej Luplertlop, Siripan Srivilairit, Polrat Wilairatana, Shigeyuki Kano, Pascal Ringwald, Sornchai Looareesuwan; Korean J Parasitol 2007;45(2):111-114.
Published online June 20, 2007; DOI: https://doi.org/10.3347/kjp.2007.45.2.111

Abstract
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Chloroquine remains the drug of choice for the treatment of vivax malaria in Thailand. Mixed infections of falciparum and vivax malaria are also common in South-East Asia. Laboratory confirmation of malaria species is not generally available. This study aimed to find alternative regimens for treating both malaria species by using falciparum antimalarial drugs. From June 2004 to May 2005, 98 patients with Plasmodium vivax were randomly treated with either artemether-lumefantrine (n = 47) or chloroquine (n = 51). Both treatments were followed by 15 mg of primaquine over 14 days. Adverse events and clinical and parasitological outcomes were recorded and revealed similar in both groups. The cure rate was 97.4% for the artemether-lumefantrine treated group and 100% for the chloroquine treated group. We concluded that the combination of artemether-lumefantrine and primaquine was well tolerated, as effective as chloroquine and primaquine, and can be an alternative regimen for treatment of vivax malaria especially in the event that a mixed infection of falciparum and vivax malaria could not be ruled out.

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