The 1st Japan-Korea Joint Workshop
Program
Poster presentations at OU Booth (Lecture room 1)
Curator:
Assoc. Prof. Manabu Suno
The 1st group (9:30-11:30)
OU-A1
Tatsuya Sakiyama
(Pharmaceutical Formulation Design)
Synchronous-Dual-Zero-Net-Flux
Microdialysis for Monitoring Focal Unbound Drug Concentration Profiles:
Improvement of Monitoring Lag.
OU-A2
Mai Takahashi
(Pharmaceutical Formulation Design)
Oral
amlodipine for dogs: Pharmaceutical modification to suppress its bitterness
OU-A3
Miki Terasaki (The Center
for Development of Advanced Pharmaceutical Education)
Effect of stem lettuce on
allergic rhinitis model in mice
OU-A4
Kenta Yagi (Clinical Pharmacy)
Differential synergistic effect of COX
inhibitors on cell survival suppressed by Sorafenib in hepatocellular cancer
cells
OU-A5
Yagi Shimpei (Clinical Pharmacy)
Influence of inflammation on
diazepam-induced sleep latency and anti-anxiety effect in mice
OU-A6
Yoneda SaoriiClinical Pharmacyj
Effect of romiplostim on impaired spatial
memory in a rat model of chemotherapy
OU-A7
Hiroko Nakamura (Clinical Pharmacy)
Ketamine exerts antidepressant - like
effects in ACTH-treated rats
OU-A8
Maki Okino (Clinical Pharmacy)
The antitumor effect of COX inhibitors
combined with Doxorubicin
OU-A9
Atsuyoshi Okada (Clinical Pharmacokinetics and Therapeutics)
Evaluation of the CNS drug sensitivity in
rats with acute renal failure
OU-A10
Shunsuke Kanetada (Biopharmaceutics)
Determinants for in-vivo anti-tumor
effects of liposomal doxorubicin (DOX)
OU-A11
Yoshihiro Sakuwa (biopharmaceutics)
Contribution of P-glycoprotein (P-gp) and
Cytochrome P450 3A (CYP3A) to Intestinal First-Pass Effect of Loperamide in
Rats
OU-A12
Takamori Aiko (Biopharmaceutics)
Basic Study for Development of New
Absorption Enhancing Formulation using Polyamine Derivatives
OU-A13
Naoki Kishi (Health Chemistry)
Function of primate
UDP-glucuronosyltransferases expressed in gastrointestinal tract
OU-A14
Yu Kinashi (Health Chemistry)
Human UDP-glucuronosyltransferase
isoforms involved in the glucuronidation of mono (2-ethylhexyl) phthalate
OU-A15
Marina Mukai (Health Chemistry)
Species and Gender Differences in
Propofol Glucuronidation
OU-A16
Satoko Watanabe (Synthetic and Medicinal Chemistry)
Synthesis of Cytotoxic Tannin Analogs for
Tumor Cells
OU-A17
Aya Takeuchi (Synthetic and Medicinal Chemistry)
Synthesis and Anti-MRSA Activity of
Indoloquinoline Derivatives
OU-A18
Mitsugu Bando (Creative Medicinal Chemistry)
Synthesis of Optically Active
Phenylpropanoic Derivatives with Fluorinated Quaternary Carbon Atom as PPAR?
Agonists
OU-A19
Yuta Tanaka (Creative Medicinal Chemistry)
Design and Synthesis of Novel PPAR? Agonists based on MD Simulations
OU-A20
Satoko AkitaiNatural Product Chemistryj
Effects of Tannins and Alkyl Gallates on Aeromonas sobria
OU-A21
Yui Arima (Natural Product Chemistry)
Constituents of White Adzuki Bean
OU-A22
Yasuyo Okame (Natural Product Chemistry)
Suppressing Effect of Tannins from Strawberry Leaves on the Norfloxacin
Resistance of MRSA
The 2nd group (13:00-15:00)
OU-B1
Watanabe Shinji (Protein Function)
Mutagenesis induced by chloroethylating
anticancer drug, and its restoration mechanism
OU-B2 Hiroki Watanabe (International Joint Research Center for Drug Discovery
on Intractable infectious Diseases)
Analysis of switching mechanisms in two
cell-death types, necrosis and apoptosis
OU-B3
Tetsuya Yamashita (Protein Function)
Inducible effect of skim milk on the
production of serine protease of Aeromonas
trota
OU-B4
Akinori Maruo (Protein Function)
Studies on the purification of the
intermediate of Aeromonas
metalloprotease
OU-B5
Noriko Tanaka (Protein Function)
Genotoxicity of UVA activated N-nitrosoproline on human derived keratinocytes
OU-B6
Ayako Maekawa (Biophysical Chemistry)
Permeability Enhancement of the Outer Membrane of Escherichia coli as
Investigated by the Rose Bengal-Induced Photoinactivation of Bacteria
OU-B7
Yuko Manabe (Biophysical Chemistry)
A study on hippocampal long-term potentiation in awake mice
OU-B8
Yuka Nakanishi (Biophysical Chemistry)
Porphyrin-Induced Photoinactication of
Bacteria and Membrane Damage of Erythrocytes
OU-B9
Miho Hyodo (Biophysical Chemistry)
Action of Amphipathic Peptides on Bacterial Cell Membranes |Relationship between Antibacterial Activity and Membrane
Permeability|
OU-B10
Aya Kakinoki (Immulobiology)
Establishment and characterization of a culture model of murine mucosal mast cells
OU-B11
Satoshi Hokari (Immunobiology)
Expression of neurotrophin receptors in murine mast cells
OU-B12
Yohei Manabe (Immunobiology)
Halogenated dinitrobenzenes induce degranulation of rat peritoneal mast cells
OU-B13
Hiroko Morinaga (Sanitary microbiology)
The genes of Cupriavidus metallidurans PD11 strain
which are expressed in degradation of dichloromethane
OU-B14
Hayata Dodan (Sanitary microbiology)
Investigation of expression control
mechanism of RND-type multidrug efflux pump in Klebsiella pneumoniae
OU-B15
Hanako Sunouchi (Sanitary microbiology)
The mobility of the genomic region around the metalloprotease gene (vvp) in Vibrio vulnificus
OU-B16
Megumi Kurata (Sanitary microbiology)
Typing of Vibrio vulnificus by genes encoding the
hemolysin and protease
OU-B17
Tsuyoshi Ito (Emergency Pharmaceutics)
Investigation of Tubal Ingestion Method
for Kampo Medicine in Advanced Critical Care Center
OU-B18
Yuka Kayano (Emergency Pharmaceutics)
Risk Factor of Acute Renal Failure Induced by Edaravone in Patients with
Cerebrovascular Disorder
OU-B19
Asuka Shiomi (Emergency Pharmaceutics)
Risk Factor of Hypotension Induced by Dexmedetomidine in the Advanced Critical
Care and Emergency Center
OU-B20
Masahiko Asano (Oncology Pharmaceutical Care)
Determination of Platinating Agents in
Human Plasma
OU-B21
Takahiro Ishino (Oncology Pharmaceutical Care)
Photodegradation of (+)-tramadol and Stability of Oral Liquid Preparations
of Tramadol
OU-B22
Kenta Sakamoto (Oncology Pharmaceutical Care)
Determination of sirolimus in human plasma
Poster presentations at SKKU Booth (Lecture room 1)
Curator:
Assoc. Prof. Yukio Sugimoto
The 1st group (9:30-11:30)
SKKU-1
Min Sang Lee (Molecular Pharmaceutics)
Enhanced Transfection by
Antioxidative Polymeric Gene Carrier that Reduces Polyplex-Mediated Cellular
Oxidative Stress
SKKU-2 Jihye Park
Pd(II)-Catalyzed
Decarboxylative Acylation of Phenylacetamides with ƒ¿-oxocarboxylic acids and
Application to the Synthesis of 3-Isochromanone
SKKU-3 Da-Young
Shin (Environmental toxicology and Preventive pharmacy)
Polyhexamethyleneguanidine phosphate induced oxidative stress-mediated
DNA damage in human A549 lung adenocarcinoma cell line
SKKU-4 Kyu-Mok
Hwang (Physical Pharmacy)
Preparation of galantamine
drug-in-adhesive patch and investigation of formulation factors affecting its
skin permeation rate
The 2nd group (13:00-15:00)
SKKU-5 Youngju Kim (Medicinal Chemistry)
Identification of Ligands
for HIV-1 RNA Stem-loop as -1 Ribosomal Frameshift Modulators by In Silico Screening
SKKU-6 Seung
Han Seon
Macrophages play a key role in the protection by Streptococcus
pneumoniae pep27 mutant vaccine
SKKU-7 Sang-Joon
Kim (Physical Pharmacy)
Investigation of
Formulation Factors for Doxazosin Mesylate Pellets
* All posters in the SKKU booth will be placed full-time.
SKKU-1
Enhanced Transfection by Antioxidative Polymeric
Gene Carrier that Reduces Polyplex-Mediated Cellular Oxidative Stress
Min Sang Lee (Molecular Pharmaceutics Lab)
Object The object of this study was to enhance transfection
efficiency using an antioxidative transfection system minimizing cellular
oxidative stress
Methods PEI-PLGA was synthesized and used as a gene carrier containing
hydrophobic antioxidant.
Cellular oxidative stress and mitochondrial membrane potential (Ģĵ) were measured by using a H2DCFDA and
JC-1, respectively. Transfection efficiency was determined by measuring a reporter gene expression level.
Results and Discussion The PEI-PLGA carried out the simultaneous delivery of antioxidant and plasmid DNA, resulting in a reduction in cellular ROS
generation and helped to maintain Ģĵ. In addition, the transfection efficiency
was dramatically increased.
Conclusion An antioxidative polymeric gene carrier
has great potential as a novel nonviral vector for gene delivery.
SKKU-2
Pd(II)-Catalyzed Decarboxylative Acylation of
Phenylacetamides with ƒ¿-oxocarboxylic acids and Application to the Synthesis of
3-Isochromanone
Jihye Park and In Su Kim
The
development of new carbon-carbon bond-forming reactions continues to be an
essential goal in organic chemistry. Traditional metal-catalyzed cross-coupling
reactions between aryl metal reagents and aryl halides are well-established
methods for the construction of C?C bonds and synthesis of complex molecules.
Recently, transition-metal-catalyzed decarboxylative cross-coupling reactions
using aryl carboxylic acids as aryl surrogates have received much attention
since such transformations provide new opportunities to use readily available
carboxylic acids as starting materials for organic synthesis.
Transition-metal-catalyzed
oxidative acylation of sp2 C?H bonds in aromatic compounds with various
directing groups, e.g., pyridines, oximes, acetanilides, and indole, with
aldehydes or alcohols were reported. However, decarboxylative C?H bond
acylations using ƒ¿-oxocarboxylic acids as acyl surrogates were relatively
unexplored. Goossen first demonstrated a palladium-catalyzed decarboxylative
crosscoupling reaction of aryl bromides with ƒ¿-keto carboxylate salts as acyl
anion equivalents to afford diaryl ketones. Ge described elegant studies on a
palladium-catalyzed decarboxylative acylation of acetanilides and
phenylpyridines with ƒ¿-oxocarboxylic acids as acyl sources via C?H bond
activation. Recently, Guo and Duan described a decarboxylative acylation of
cyclic enamides with ƒ¿-oxocarboxylic acids to provide ƒÀ-acyl enamides.
Herein we described our recent result on a Pd-catalyzed decarboxylative
ortho-acylation of O-methyl ketoximes and phenylacetamides with ƒ¿-keto
acids via C?H bond activation. This protocol provides an efficient access
to a range of ortho-acyl phenylacetamides, which can be easily converted
to 3-isochromanone derivatives.
SKKU-3
Polyhexamethyleneguanidine phosphate induced
oxidative stress-mediated DNA damage in human A549 lung adenocarcinoma cell
line
Da-Young Shin (Laboratory
of Environmental toxicology and Preventive pharmacy)
[Object] Recently
household chemicals exposure by inhalation has been increased and its health
effects became emerging issue. Especially, in Korea, the major component of
humidifier disinfectant, polyhexamethy- leneguanidine phosphate (PHMG) caused
deaths through lung fibrosis. However, the mechanism under the fibrosis is
still unknown. In this study, the oxidative stress and DNA damage of PHMG was
investigated in human A549 lung adenocarcinoma cell line, to study the
potential role of DNA damage in PHMG-induced fibrosis.
[Methods] First, the
cytotoxic effect of PHMG was assessed by WST-1 assay. Second, cells were
exposed to PHMG for 6 hours after which ROS generation was measured by DCF-DA
assay. Lastly, Oxidative stress-mediated DNA damage by PHMG was studied via
modified comet assay.
[Results and Discussion] After 24 h exposure, cell viability was dose-dependently reduced by PHMG,
and partially increased with the treatment of deferoxamine. PHMG significantly
promoted ROS generation and this is partially inhibited by N-acetyl-L-cysteine.
In addition, oxidative DNA damage was detected in cells exposed to PHMG.
[Conclusion] In conclusion, the PHMG induced oxidative stress in human lung cells,
and this effect can be followed by DNA damage. Through this study, the
potential role of DNA damage in PHMG-induced fibrosis was observed. Further,
expression of specific genes related to fibrosis will be assessed.
SKKU-4
Preparation of galantamine drug-in-adhesive
patch and investigation of formulation factors affecting its skin permeation
rate
Kyu-Mok Hwang (Physical
Pharmacy Lab.)
[Object] To prepare
galantamine drug-in-adhesive (GLT DIA) transdermal patch and to investigate the
effect of API salt form, concentration and type of pressure sensitive adhesives
(PSA) on its skin permeation rate.
[Methods] The target permeation rate of
galanatmine through the skin was decided by using a simulation software (ScientistR,
MicroMath Research, USA). The GLT DIA patches were prepared by dissolving the
drug into ethanol and then mixing with PSA solution using mechanical stirrer.
The drug-PSA solution was coated on a polyester released liner using a coating
unit (Labcoater LTE-S, Mathis AGE, Oberhasli, Switzerland) and laminated with a
polyester backing film. In vitro skin
permeation test was done using Franz diffusion cells. In vivo transdermal drug delivery was done after application to New
Zealand white rabbits weighing 1.8-2 kg. The amounts of galantamine in plasma
or receptor medium were determined by a validated HPLC method. The correlation
of in vivo permeation rate and in vitro permeation rate by type of PSA
was also determined.
[Results and
Discussion] The target
permeation rate of GLT DIA was between 10 ƒÊg/cm2Eh and 100 ƒÊg/cm2Eh considering
the interspecies differences between human and animals. Acrylate PSA was
divided into three groups according to their functional groups: carboxyl group,
hydroxyl group, and no functional group. Among them, the PSA group having
hydroxyl functional group, and especially DT-2510 showed the highest permeation
rate (12.60 } 3.31 ƒÊg/cm2Eh). This result had similar result in
rank with in vivo study on rabbits, in
which AUC0-24 by PSA types is written in decreasing order: hydroxyl
group, no functional group, carboxyl group. This can be explained by less
drug-polymer interaction, resulting in faster drug diffusion rates. The
concentration of drug in GLT DIA patches was proportional to the permeation
rate, which is explained by the Fickfs diffusion law. The prepared GLT DIA
showed better pharmacokinetic properties compared to oral solution or IV
injection. The mean residence time of all GLT DIA patches ( -OH: 8.40 } 2.87 h, -COOH: 17.64 } 3.01 h, None: 15.07 } 2.08 h) were higher than IV injection (0.37}0.05 h) and oral solution 0.85 }0.18 h). The absolute bioavailability GLT DIA( -OH: 80.30%,
-COOH: 41.78%, None: 55.98%)was also higher than oral solution (21.52%)
[Conclusion] GLT DIA patches have advantages over
oral solution in terms of bioavailability and MRT which results in higher
patient compliance. The high correlation of in
vivo profiles and in vitro
profile by type of PSA can be a useful tool in determining selection of PSA at
preliminary investigation.
SKKU-5
Macrophages play a key role in the protection by Streptococcus pneumoniae pep27 mutant
vaccine
Youngju Kim,a* Junghyun Chae,b So-Jung Park,a and
Hyun-Ju Parka
aMedicinal
Chemistry Laboraotry, School of Pharmacy, Sungkyunkwan University,
bDepartment
of Chemistry, Sungshin Womenfs University
[Object] The aim of
this project is to discover novel ligands for HIV-1 RNA stem-loop by
structure-based virtual screening of chemical database. HIV-1 requires a programmed -1
ribosomal frameshifting (-1 RF) for expressing Gag and Gag-Pol fusion protein, of which ratio is critical for HIV-1 replication.
The -1 RF is induced by HIV-1 RNA stem-loop and the stability of stem-loop
is important in maintaining efficient -1 RF. Thus, a small molecule that
changes the -1 RF efficiency by interacting with RNA stem-loop, can be
developed as an anti- HIV-1 agent.
[Methods] To select the candidate ligands targeting HIV-1 RNA stem-loop, first,
the Unity 3D (Sybyl-X 2.0, Tripos Inc.) search of chemical database including
ZINC and in-house was carried out using a pharmacophore query. This query
was established based on the NMR solution structure of HIV-1 RNA stem-loop
in complex with known ligand RG501. Next, virtual screening of the primary
focused library was performed by using automated docking program, AutoDock_Vina.
After virtual screening, the final candidate compounds were selected by
considering docking score and docking poses. The effects of compounds on
-1 RF were tested by in vitro -1 transcription/translation coupled assay(TNT),
and the -1 RF efficiencies were measured by dual luciferase assay (DLA),
and SDS-PAGE.
[Results and Discussion] As a result of docking analysis, we filtered 244 of candidate compounds. Dataset
was docked into the binding site of HIV-1 stem-loop. Among 244 compounds, 36
compounds were selected by docking score and visual inspection. Next, we
measured the -1 RF efficiency values in the presence of candidate compounds by
DLA. Three compounds (SC13, SC16, and SC32) dramatically decreased -1 RF
efficiency about 60 ? 90 %. Among them, SC16 showed strong inhibition effect,
and the IC50 value was 1.37 ƒÊM. In addition, we also confirmed that SC16 particularly decreased -1 RF
by cell-based -1 RF assay.
[Conclusion] Through this
study, we identify a small molecule ligand SC16 for HIV-1 RNA stem-loop which
inhibits the -1 frameshifting in HIV-1.
SC16 may serve as a lead compound to develop potential anti-frameshifting
agents against HIV-1.
SKKU-6
Macrophages play a key role in the protection by Streptococcus pneumoniae pep27 mutant
vaccine
Seung Han Seon1, Sang-Yoon Choi1,
David E. Briles2, Suhkneung Pyo1, Dong-Kwon Rhee1
1School of Pharmacy, Sungkyunkwan University;
2Department of Microbiology,
University of Alabama at Birmingham
Streptococcus pneumoniae is responsible for high
mortality, causing various invasive pneumococcal diseases. Since several problems
such as serotype shifts have been found despite introduction of current
pneumococcal vaccine, a new type of vaccine is needed to solve these problems. Previously, intranasal immunization of the pep27 mutant showed protection against heterologous
lethal challenge indicating that the mutant could be a highly feasible vaccine
candidate. To elucidate the underlying mechanism of the protection, humoral and
cellular responses in immunized and non-immunized groups were compared. Although
the level of IgG in the immunized group was significantly increased, there was
no passive-immunity against lethal D39 challenge. Moreover, when CD4+ and CD8+
T cells were depleted from the immunized mice followed by lethal challenge, the
mice did not show mortality whereas non-immunized group did indicating that T
cells may not be involved in the protection. However, BALF from the immunized
mice showed significantly higher level of IFN-ƒÁ when exposed to D39, indicating
the involvement of IFN-ƒÁ-activated macrophages.
In in vitro study, phagocytic
activities of bone marrow-derived macrophages from the immunized mice were
significantly increased when exposed to D39 compared to non-immunized group. In
addition, flow cytometric assay showed spleen-derived monocytes from the
immunized mice differentiated much rapidly into macrophages than those from the
non-immunized group. Overall, these results suggested that IFN-ƒÁ-activated
macrophages, but not T and B cells, could be important for the protection from
lethal infection after i.n.
immunization with the pep27 mutant.
SKKU-7
Investigation of Formulation Factors
for Doxazosin Mesylate Pellets
Sang-Joon Kim, (Physical Pharmacy Lab.)
[Object] The aims of the present study were to prepare doxazosin mesylate (DXM)
pellets coated by fluid-bed coater and to compare the effect of coating level,
coating agents and plasticizers on its dissolution rate.
[Methods] The doxazosin
mesylate (DXM) core pellets were prepared by the extrusion-spheronization
technique. The surface morphology of the core pellets and that of the coated
pellets were examined by scanning electron microscopy (SEM, JSM-35CF, Jeol,
Japan). To control dissolution rate of DXM from the pellets, the core pellets
prepared were coated with a coating dispersions containing EudragitR
RL PO/RS PO and plasticizers using a fluid-bed
coater (Model D-7852, Glatt GmbH, Germany).
The dissolution rates of DXM from the pellets were
measured using an USP apparatus 2 (DST-600A, Labfine Inc., Korea) at 37}0.5‹C, and stirring rate was 75 rpm. The dissolution medium was simulated
gastric fluids without enzymes (pH1.2). The dissolution study of DXM pellets
was performed to examine the effect of EudragitR RL PO and RS PO on sustained release. The effect of coating level on the
dissolution rate was also evaluated, since it could affect directly on
dissolution rate of drug. The amount of the drug released from the pellets
was analyzed by using HPLC system (7000 series, Hitachi Ltd., Japan).
[Results and Discussion] The morphology
of DXM pellets were examined by SEM. The
core pellets were shown to have a regular spherical shape and slightly rough
surface. DXM pellets were coated successfully and the coating process by
fluid-bed coater was appropriate for subsequent experiments. The uniform coating layer was observed at both ratios
and the coating layer got thicker as the coating layer got thicker a s the
coating ratio increased. The pellets coated with PEG 6000 or TEC as a
plasticizer, showed a smooth surface and the coating layer was well formed. On
the other hand, the pellets coated with castor oil showed cracks on the surface.
The dissolution rate had slowed down gradually for
both of EudragitR RL PO and RS PO as the coating level had
increased. However, the sustained-release effect of EudragitR RS PO
was much stronger than RL PO and the difference had increased distinctly as the
coating level had increased. The differences of the effect on dissolution rate came
from distinction of property. EudragitR RS PO had a slightly water
permeable property, whereas, EudragitR RL PO had a highly permeable characteristic.
The effect of the plasticizer content ratio on the
release of DXM was examined in the coated pellets with EudragitR RS
PO by 2.5% coating level. The increasing concentration of plasticizers in
coating solution generally shows decreased drug release profiles. The pellets
coated with TEC showed the slowest dissolution rate, on the other hand, those
coated with PEG 6000 showed a moderate sustained effect PEG 6000 is more
soluble in water than TEC, so as less of a water soluble plasticizer, TEC, is
more compatible with EudragitR RS PO which is insoluble in water. As
a result, the release of DXM from pellets coated with TEC was slower than PEG
6000, so it was chosen as the plasticizer.
[Conclusion] The prepared pellets were a regular spherical shape, and showed a uniform
coating layer according to the coating level. The coating thickness is a very important
factor to control the release of DXM from coated pellets. The effect on a
sustained-release of EudragitR RS PO is much higher, compared with
EudragitR RL PO. The plasticizer also could control the release of
DXM from pellets coated with EudragitR RS PO but the effect of
plasticizers in EudragitR RL PO is weaker as compared to EudragitR
RS PO.