• Biomolecules & Therapeutics
• /
• v.32 no.5
• /
• pp.540-545
• /
• 2024

In this study, the potential effects of pyronaridine, an antimalarial agent, on airway MUC5AC mucin gene expression were investigated. The human pulmonary epithelial NCI-H292 cells were pretreated with pyronaridine for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of pyronaridine on the PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also examined. Pyronaridine inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA through the inhibition of degradation of inhibitory kappa Bα and NF-κB p65 nuclear translocation. These results suggest that pyronaridine suppresses gene expression of mucin through regulation of the NF-κB signaling pathway in human pulmonary epithelial cells.

• Bulletin of the Korean Chemical Society
• /
• v.35 no.2
• /
• pp.521-524
• /
• 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
• /
• v.53 no.1
• /
• pp.35-41
• /
• 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.

• Journal of Radiation Industry
• /
• v.7 no.2_3
• /
• pp.221-224
• /
• 2013

RI-Biomics is a new compound word of radiation technology and Biomics related to the study of life. RI-Biomics is high radiation fusion technology by combining evaluation of pharmacokinetics in vivo (RI-ADME) of new drugs and medical materials using radioisotope and molecular imaging technology using nuclear medicine equipments. RI-Biomics fields are emerging with the increasing usage of radioisotopes (RI). In this paper, we investigated the latest trends of radioisotope using in RI-Biomics fields. The representative radioisotopes are $^{14}C$, $^3H$ and $^{32}P$ for the optimization and the selection of candidates in the development process of new drugs among the RI-Biomics fields. As shown in the status of accumulated income of radioisotopes, using amounts of radioisotopes are showing a tendency to increase every year. $^{14}C$ is 61.6% increase of accumulated income growth rate and $^3H$ increased by 58.8% and $^{32}P$ increased by 33.9% in 2012 compared to 2007. These isotopes are used in a variety of fields as using of $^{14}C$ for microdosing test, development of [$^3H$]cholesterol absorption inhibitors, study of [$^{131}I$]pyronaridine tetraphosphate for malaria therapy. These are going on in vivo test sucessfully. So, clinical research step is expected to begin soon. Therefore, usages of radioisotopes are necessary and need for the evaluation of pharmacokinetics, optimization and the selection of new drug candidates in the development process of new drugs among the RI-Biomics fields. So, using of radioisotopes is predict to increase continuously except for primarily used $^{14}C$, $^3H$.