• Analytical Science and Technology
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• v.22 no.1
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• pp.101-108
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• 2009

The bioequivalence of two pioglitazone tablets, Actos$^{(R)}$ tablet (Takeda Chemical Industries, reference drug) and Pioglitazone tablet (Boryung Company, test drug) was evaluated according to the guidelines of Korea Food and Drug Administration. Twenty-eight healthy male Korean volunteers received each medicine (pioglitazone dose of 30 mg) in a $2{\times}2$ crossover study with one week washout interval. After drug administration, blood samples were collected at specific time intervals from 0-36 hours. The plasma concentrations of pioglitazone were determined by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total chromatographic run time was 5 min and calibration curves were linear over the concentration range of 5-2000 ng/mL for pioglitazone. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The primary calculated pharmacokinetic parameters were compared statistically to evaluate bioequivalence between the two preparations. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Pioglitazone tablet and Actos$^{(R)}$ tablet were log0.9422~log1.1040 and log0.9200~log1.1556, respectively. Based on the statistical considerations, we can conclude that the test drug, Pioglitazone tablet was bioequivalent to the reference drug, Actos$^{(R)}$ tablet.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2004.11a
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• pp.203-209
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• 2004

Molecular docking using Lamarckian genetic algorithm of AutoDock 3.0 (AD3) was employed to understand in retrospect the selectivity of phenylaminopyrimidine (PAP) derivatives against the kinase domain c-Abl, implicated in chronic myelogenous leukemia (CML). The energetics of protein-ligand complex was scored using AD3 to identify active drug conformations while Ligplot and ligand protein contact (LPC) programs were used to probe schematic molecular recognition of the bound inhibitor to the protein. Results signify correlation between model and crystal structures of STI-571 compound or Imatinib (IM), a PAP derivative and now clinically proven for its efficacy in CML. A prospect active form Abl inhibitor scaffold from matlystatin class of compounds will be published elsewhere.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2286-2300
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• 2011

We synthesized eight G8 molecular transporters (MTs) based on 4 different monosaccharide scaffolds, and studied their biological properties with a special focus on possible mitochondrial targeting and tissue selectivity. The mitochondrial affinity of these MTs was found to be clearly related to the scaffold stereochemistry and also tenuously with the lipophilicity. It may be suggested that in the practical delivery strategy of drugs for the brain and mitochondrial diseases the BBB permeability and mitochondrial affinity should be considered as key parameters, and that an enhanced mitochondrial affinity appears possible by further research on the structure-property relationship of guanidine-rich molecular transporters.

• BMB Reports
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• v.46 no.2
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• pp.97-102
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• 2013

The use of various cancer cell lines can recapitulate known tumor-associated mutations and genetically define cancer subsets. This approach also enables comparative surveys of associations between cancer mutations and drug responses. Here, we analyzed the effects of ~40,000 compounds on cancer cell lines that showed diverse mutation-dependent sensitivity profiles. Over 1,000 compounds exhibited unique sensitivity on cell lines with specific mutational genotypes, and these compounds were clustered into six different classes of mutation-oriented sensitivity. The present analysis provides new insights into the relationship between somatic mutations and selectivity response of chemicals, and these results should have applications related to predicting and optimizing thera-peutic windows for anti-cancer agents.

• Smart Structures and Systems
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• v.7 no.3
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• pp.185-198
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• 2011

The promise of biomimetic smart structures that can function as sensors and actuators in biomedicine is enormous. Technological development in the field of stimuli-responsive shape memory polymers have opened up a new avenue of applications for polymer-based synthetic actuators. Such synthetic actuators mimic various attributes of living organisms including responsiveness to stimuli, shape memory, selectivity, motility, and organization. This article briefly reviews various stimuli-responsive shape memory polymers and their application as bioactuators. Although the technological advancements have prototyped the potential applications of these smart materials, their widespread commercialization depends on many factors such as sensitivity, versatility, moldability, robustness, and cost.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.29-33
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• 2001

A method for the determination of anionic drug, mefenamate with ion-selective electrode using Fe(II)-1,10-phenanthroline chelate as a counter ion was developed. Benzyl nitrophenyl ether (BNPE) plasticized membrane was more selective and sensitive than the other tested membranes. This membrane electrode exhibits a linear response for 10$^{-2}$ M~5 $\times$ 10$^{-5}$ M of mefenamic acid with a slope of -61.4 mV/dec. in borate buffer solutions (pH 9.0). Potentiometric selectivity measurements revealed negligible interferences from various organic and ionorganic anions. Direct potentiometry and potentiometric titration method of mefenamic acid in capsule preparations are presented and compared.

• YAKHAK HOEJI
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• v.43 no.3
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• pp.289-293
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• 1999

Many poly (vinyl chloride : PVC) membrane electrodes were investigated for the determination of basic drugs, chlorpromazine, amitriptyline, nortriptyline, etc. These electrodes are based on the use of the ion-association complexes of the basic drugs with eriochrome cyanine R, chromoxane cyanine, chrome azurol S and picric acid as ion-exchange sites in a plasticized PVC matrix. All ion-exchangers except picrate complex were not proper for use, because those complexes in plasticized membrane were excluded into aqueous working solution. These drug electrodes show excellent Nernstian responses in the concentration ranges $10^{-2}~10^{-6}$ mol $dm^{-3}$. Their selectivity with respect to each other, as well as their work-able pH range have been investigated. The major advantages of the proposed methods are their simplicity and speed.

• Bulletin of the Korean Chemical Society
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• v.30 no.2
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• pp.343-347
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• 2009

In this study, the surface of inorganic fine powders is hybridized with nanovesicles containing tocopheryl acetate prepared with hydrogenated lecithin via a coating process. From AFM and SEM analyses it is found that the surface of the nanovesicle-coated fine powders lost their traditional topology and improved in terms of their roughness, skewness, and kurtosis. In addition, TEM observations revealed the formation of a 5 nm thick coating layer on the surface of the fine powders. These hybridized powders, in which bioactive materials such as tocopheryl acetate can be embedded, can be employed as a part of a drug delivery system due to their special ability to control release rate and temperature selectivity. Physical properties of the powders, i.e., the different angle and friction coefficient, were excellent.

• Molecules and Cells
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• v.20 no.1
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• pp.1-16
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• 2005

The peptidyl transferase center (PTC) is located in a protein free environment, thus confirming that the ribosome is a ribozyme. This arched void has dimensions suitable for accommodating the 3'ends of the A-and the P-site tRNAs, and is situated within a universal sizable symmetry-related region that connects all ribosomal functional centers involved in amino-acid polymerization. The linkage between the elaborate PTC architecture and the A-site tRNA position revealed that the A-to P-site passage of the tRNA 3'end is performed by a rotatory motion, which leads to stereochemistry suitable for peptide bond formation and for substrate mediated catalysis, thus suggesting that the PTC evolved by genefusion. Adjacent to the PTC is the entrance of the protein exit tunnel, shown to play active roles in sequence-specific gating of nascent chains and in responding to cellular signals. This tunnel also provides a site that may be exploited for local co-translational folding and seems to assist in nascent chain trafficking into the hydrophobic space formed by the first bacterial chaperone, the trigger factor. Many antibiotics target ribosomes. Although the ribosome is highly conserved, subtle sequence and/or conformational variations enable drug selectivity, thus facilitating clinical usage. Comparisons of high-resolution structures of complexes of antibiotics bound to ribosomes from eubacteria resembling pathogens, to an archaeon that shares properties with eukaryotes and to its mutant that allows antibiotics binding, demonstrated the unambiguous difference between mere binding and therapeutical effectiveness. The observed variability in antibiotics inhibitory modes, accompanied by the elucidation of the structural basis to antibiotics mechanism justifies expectations for structural based improved properties of existing compounds as well as for the development of novel drugs.

• Parasites, Hosts and Diseases
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• v.54 no.2
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• pp.155-161
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• 2016

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.