• Parasites, Hosts and Diseases
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• v.42 no.2
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• pp.61-66
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• 2004

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.

• Parasites, Hosts and Diseases
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• v.60 no.5
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• pp.339-344
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• 2022

The development of drug resistance is one of the most severe concerns of malaria control because it increases the risk of malaria morbidity and death. A new candidate drug with antiplasmodial activity is urgently needed. This study evaluated the efficacy of different dosages of aqueous extract of Strychnos ligustrina combined with dihydroartemisinin and piperaquine phosphate (DHP) against murine Plasmodium berghei infection. The BALB/c mice aged 6-8 weeks were divided into 6 groups, each consisting of 10 mice. The growth inhibition of compounds against P. berghei was monitored by calculating the percentage of parasitemia. The results showed that the mice receiving aqueous extract and combination treatment showed growth inhibition of P. berghei in 74% and 94%, respectively. S. ligustrina extract, which consisted of brucine and strychnine, effectively inhibited the multiplication of P. berghei. The treated mice showed improved hematology profiles, body weight, and temperature, as compared to control mice. Co-treatment with S. ligustrina extract and DHP revealed significant antimalarial and antipyretic effects. Our results provide prospects for further discovery of antimalarial drugs that may show more successful chemotherapeutic treatment.

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.405-409
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• 2019

In malaria, splenic rupture is a serious complication potentially leading to death. Subcapsular hemorrhage of spleen is thought to be an impending sign of splenic rupture; however, the characteristics of subcapsular hemorrhage are not well known. We report 3 cases of subcapsular hemorrhage of the spleen in vivax malaria, with varying degrees of severity. Case 1 showed subcapsular hemorrhage without splenic rupture, was treated by antimalarial drug without any procedure. The healing process of the patient's spleen was monitored through 6 computed tomography follow-up examinations, over 118 days. Case 2 presented subcapsular hemorrhage with splenic rupture, treated only with an antimalarial drug. Case 3 showed subcapsular hemorrhage with splenic rupture and hypotension, treated using splenic artery embolization. They all recovered from subcapsular hemorrhage without any other complications. These 3 cases reveal the process of subcapsular hemorrhage leading to rupture and a potentially fatal outcome. The treatment plan of subcapsular hemorrhage should be determined carefully considering the vital signs, changes in hemoglobin, and bleeding tendency.

• Bulletin of the Korean Chemical Society
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• v.35 no.2
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• pp.521-524
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• 2014

Pyronaridine tetraphosphate (1) is a well-known antimalarial drug. However, it required a carefully optimized production process for the manufacture of pyronaridine tetraphosphate. Each step of its manufacturing process was reinvestigated. For the cyclization of 4-chloro-2-(6-methoxy-pyridin-3-yl-amino)-benzoic acid 6 to 7,10-dichloro-2-methoxybenzo[b]-1,5-naphthyridine 5, an improved process was developed to eliminated critical process impurity (BIA). By the redesign of the formation of triphosphate salt, the purity as API grade was increased. Thus, a robust manufacturing process with an acceptable process performance has been developed to produce high quality pyronaridine tetraphosphate.

• Parasites, Hosts and Diseases
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• v.53 no.1
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• pp.35-41
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• 2015

Pyronaridine and artesunate have been shown to be effective in falciparum malaria treatment. However, pyronaridine is rarely used in Hainan Island clinically, and artesunate is not widely used as a therapeutic agent. Instead, conventional antimalarial drugs, chloroquine and piperaquine, are used, explaining the emergence of chloroquine-resistant Plasmodium falciparum. In this article, we investigated the sensitivity of P. falciparum to antimalarial drugs used in Hainan Island for rational drug therapy. We performed in vivo (28 days) and in vitro tests to determine the sensitivity of P. falciparum to antimalarial drugs. Total 46 patients with falciparum malaria were treated with dihydroartemisinin/piperaquine phosphate (DUO-COTECXIN) and followed up for 28 day. The cure rate was 97.8%. The mean fever clearance time ($22.5{\pm}10.6hr$) and the mean parasite clearance time ($27.3{\pm}12.2hr$) showed no statistical significance with different genders, ages, temperatures, or parasite density (P>0.05). The resistance rates of chloroquine, piperaquine, pyronarididine, and artesunate detected in vitro were 71.9%, 40.6%, 12.5%, and 0%, respectively (P<0.0001). The resistance intensities decreased as follows: chloroquine>piperaquine>pyronarididine>artesunate. The inhibitory dose 50 ($IC_{50}$) was $3.77{\times}10^{-6}mol/L$, $2.09{\times}10^{-6}mol/L$, $0.09{\times}10^{-6}mol/L$, and $0.05{\times}10^{-6}mol/L$, and the mean concentrations for complete inhibition (CIMC) of schizont formation were $5.60{\times}10^{-6}mol/L$, $9.26{\times}10^{-6}mol/L$, $0.55{\times}10^{-6}mol/L$, and $0.07{\times}10^{-6}mol/L$, respectively. Dihydroartemisinin showed a strong therapeutic effect against falciparum malaria with a low toxicity.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.45-45
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• 2003

The present study was conducted to investigate the potential embryo-fetal toxicity of Artesunate, an antimalarial drug, in Sprague-Dawley rats. The test item was orally administered by gavage to pregnant rats (22 females per group) from days 6 through 15 of gestation at dose levels of 0, 2, 4 and 8 mg/kg/ day. (omitted)

• Korean Journal of Pharmacognosy
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• v.22 no.3
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• pp.145-155
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• 1991

Peroxides in natural products have been recently received a considerable attention due to their various biological and pharmacological properties. Nearly 300 peroxides have been isolated and structually characterized from natural sources, mainly as constituents of Compositae and marine sponge, and occur randomly in about 10 other plant families. Among peroxides studied, sesquiterpene endoperoxide, quinghaosu, has been already clinically applied as a new antimalarial drug. Based on the peroxides reported, structural classification, natural distribution and biological and pharmacological activities are reviewed. Color reagent and spectroscopic identification of peroxide are also described.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.315.2-315.2
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• 2002

The translationally controlled tumor-associated proteins (TCTPs) are a highly conserved and abundantly expressed family of eukaryotic proteins that are implicated in both cell growth and human acute allergic response but whose intracellular biochemical function has remained elusive. There are reports that antimalarial drug, artemisinin. binds to Plasmodium falciparum TCTP. however, its 3D structure has not been known. (omitted)

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.369-377
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• 2019

Artemisinin-based combination therapy (ACT) resistance is widespread throughout the Greater Mekong Subregion. This raises concern over the antimalarial treatment in Thailand since it shares borders with Cambodia, Laos, and Myanmar where high ACT failure rates were reported. It is crucial to have information about the spread of ACT resistance for efficient planning and treatment. This study was to identify the molecular markers for antimalarial drug resistance: Pfkelch13 and Pfmdr1 mutations from 5 provinces of southern Thailand, from 2012 to 2017, of which 2 provinces on the Thai- Myanmar border (Chumphon and Ranong), one on Thai-Malaysia border (Yala) and 2 from non-border provinces (Phang Nga and Surat Thani). The results showed that C580Y mutation of Pfkelch13 was found mainly in the province on the Thai-Myanmar border. No mutations in the PfKelch13 gene were found in Surat Thani and Yala. The Pfmdr1 gene isolated from the Thai-Malaysia border was a different pattern from those found in other areas (100% N86Y) whereas wild type strain was present in Phang Nga. Our study indicated that the molecular markers of artemisinin resistance were spread in the provinces bordering along the Thai-Myanmar, and the pattern of Pfmdr1 mutations from the areas along the international border of Thailand differed from those of the non-border provinces. The information of the molecular markers from this study highlighted the recent spread of artemisinin resistant parasites from the endemic area, and the data will be useful for optimizing antimalarial treatment based on regional differences.

• Toxicological Research
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• v.26 no.3
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• pp.223-232
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• 2010

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.