• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2001.05c
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• pp.143-147
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• 2001

Ferromagnetism in manganese compound semiconductors open prospects for tailoring magnetic and spin-related phenomena in semiconductors with a precision specific to III-V compounds. Also it addresses a question about the origin of the magnetic interactions that lead to a Curie temperature(Tc) as high as 110 K for a manganese concentration of just 5%. Zener's model of ferromagnetism, originally suggested for transition metals in 1950, can explain Tc of $Ga_{1-x}Mn_x$ As and that of its IT-VI counterpart $Zn_{1-x}Mn_x$ Te and is used to predict materials with Tc exceeding room temperature, an important step toward semiconductor electronics that use both charge and spin. In this article, we present not only the experimental result but calculated Curie temperature by RKKY interaction. The problem in making III-V semiconductor has been the low solubility of magnetic elements, such as manganese, in the compound, since the magnetic effects are roughly proportional to the concentration of the magnetic ions. Low solubility of magnetic elements was overcome by low-temperature nonequilibrium MBE{molecular beam epitaxy) growth, and ferromagnetic (Ga,Mn)As was realized. Magnetotransport measurements revealed that the magnetic transition temperature can be as high as 110 K for a small manganese concentration.

• YAKHAK HOEJI
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• v.60 no.3
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• pp.135-140
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• 2016

Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone, which is associated with stabilization of many oncogenic proteins for cancer cell survival. Hsp90 is overexpressed 2-10 fold higher in cancer cells than normal cells. Due to its potential to simultaneously disable multiple signaling pathway, Hsp90 has been identified as a validated target for cancer therapy. Accordingly, we designed and synthesized 2',4'-dimethoxychalcone derivatives to inhibit Hsp90 chaperone function. Among 2',4'-dimethoxychalcone derivatives, we found that compound 1g disrupted Hsp90 chaperoning function and impaired the growth of cancer cells. These findings indicated that 1g could serve a potential lead compound to target Hsp90 in cancer chemotherapy.

• Archives of Pharmacal Research
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• v.20 no.2
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• pp.138-143
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• 1997

5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines were reported to have strong antitumor activity and one of the derivatives such as $5-[4^{l}$ -(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a] isoquinoline (1, SDZ 62-434) was found to be more effective than the clinical cytostatic agent edelfosine (2) in in vitro and in vivo assays. Currently SDZ 62-434 is in clinical trials in Europe. The structure-activity relationship studies of SDZ 62-434 showed that compounds with substitution on ring A were less active than the lead compound. Ring B in SDZ 62-434 was essential for the activity because compounds without B ring had no antitumor activity. Among the 3-arylisoquinolin-1-one derivatives, $3-[4^{I}$-(piperidinomethyl)phenyl] substituted analog had no antitumor activity but simple phenyl substituted compound, such as 4, showed the most potent antitumor activity in various human tumor cell lines.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3629-3634
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• 2012

A series of new 4-(pyridin-4-yl)-(3-methoxy-5-methylphenyl)-1H-pyrazoles (6a-k & 7a-l) has been rationally designed based on the structure of the lead compound KIST301080, a selective ROS receptor tyrosine kinase inhibitor, in order to study the activity of ROS of this new class of inhibitors. The compounds were synthesized and screened against ROS kinase, where compound 6h showed moderate inhibitory activity with an $IC_{50}$ value of $6.25{\mu}M$. The study emphasized the importance of the acetonitrile group at the pyrazole ring and also the importance of having a hydrogen bond donor on the distal phenyl ring linked to the pyridine moiety.

• Bulletin of the Korean Chemical Society
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• v.34 no.8
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• pp.2297-2304
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• 2013

A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 ($IC_{50}=1.08{\mu}g/mL$, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.270-275
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• 2001

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (birding assay) for NMDA receptor glycine site.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.191-199
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• 2000

Genomics is providing targets faster than we can validate them and combinatorial chemistry is providing new chemical entities faster than we can screen them. Historically, the drug discovery cascade has been established as a sequential process initiated with a potency screening against a selected biological target. In this sequential process, pharmacokinetics was often regarded as a low-throughput activity. Typically, limited pharmacokinetics studies would be conducted prior to acceptance of a compound for safety evaluation and, as a result, compounds often failed to reach a clinical testing due to unfavorable pharmacokinetic characteristics. A new paradigm in drug discovery has emerged in which the entire sample collection is rapidly screened using robotized high-throughput assays at the outset of the program. Higher-throughput pharmacokinetics (HTPK) is being achieved through introduction of new techniques, including automation for sample preparation and new experimental approaches. A number of in vitro and in vivo methods are being developed for the HTPK. In vitro studies, in which many cell lines are used to screen absorption and metabolism, are generally faster than in vivo screening, and, in this sense, in vitro screening is often considered as a real HTPK. Despite the elegance of the in vitro models, however, in vivo screenings are always essential for the final confirmation. Among these in vivo methods, cassette dosing technique, is believed the methods that is applicable in the screening of pharmacokinetics of many compounds at a time. The widespread use of liquid chromatography (LC) interfaced to mass spectrometry (MS) or tandem mass spectrometry (MS/MS) allowed the feasibility of the cassette dosing technique. Another approach to increase the throughput of in vivo screening of pharmacokinetics is to reduce the number of sample analysis. Two common approaches are used for this purpose. First, samples from identical study designs but that contain different drug candidate can be pooled to produce single set of samples, thus, reducing sample to be analyzed. Second, for a single test compound, serial plasma samples can be pooled to produce a single composite sample for analysis. In this review, we validated the issue whether the second method can be applied to practical screening of in vivo pharmacokinetics using data from seven of our previous bioequivalence studies. For a given drug, equally spaced serial plasma samples were pooled to achieve a 'Pooled Concentration' for the drug. An area under the plasma drug concentration-time curve (AUC) was then calculated theoretically using the pooled concentration and the predicted AUC value was statistically compared with the traditionally calculated AUC value. The comparison revealed that the sample pooling method generated reasonably accurate AUC values when compared with those obtained by the traditional approach. It is especially noteworthy that the accuracy was obtained by the analysis of only one sample instead of analyses of a number of samples that necessitates a significant man-power and time. Thus, we propose the sample pooling method as an alternative to in vivo pharmacokinetic approach in the selection potential lead(s) from combinatorial libraries.

• Journal of Life Science
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• v.25 no.1
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• pp.53-61
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• 2015

In this study, we tried to separate the photosensitizer that induces apoptosis of leukemia cells (U937) from perilla leaves. Perilla leaves (Perilla frutescens Britt var. japonica Hara) are a popular vegetable in Korea, being rich in vitamins (A and E), GABA, and minerals. Dried perilla leaves were extracted with methanol to separate the photosensitizer by various chromatographic techniques. The structure of the isolated compound (PL9443) was identified by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. Absorbance of the UV-Vis spectrum was highest at 410 nm and was confirmed by the 330, 410, and 668 nm. PL9443 compound was determined to be pheophorbide, an ethyl ester having a molecular weight of 620. It was identified as a derivative compound of pheophorbide structure when magnesium comes away from a porphyrin ring. Observation of morphological changes in U937 cells following cell death induced by treated PL9443 compound revealed representative phenomena of apoptosis only in light irradiation conditions (apoptotic body, vesicle formation). Results from examining the cytotoxicity of PL9443 substance against U937 cells showed that inhibition rates of the cell growth were 99.9% with the concentration of 0.32 nM PL9443. Also, the caspase-3/7 activity was 99% against U937 cells with the concentration of 0.08 nM of PL9443 substance. The result of the electrophoresis was that a DNA ladder was formed by the PL9443. The PL9443 compound is a promising lead compound as a photosensitizer for photodynamic therapy of cancer.

• Journal of Soil and Groundwater Environment
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• v.17 no.6
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• pp.82-91
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• 2012

The heavy metal effects on the degradation of fluorene by Sphingobacterium sp. KM-02 was determined in liquid cultures. The results showed that 10 mg/L cadmium, copper, zinc, and lead not only affected the growth of KM-02 with fluorene but also the ability of growing or resting cells to degrade this compound. Growth and fluorene degradation were strongly inhibited by cadmium and copper at 10 mg/L, while the inhibitory effect of zinc and lead at the same concentration or at 100 mg/L were not significant. In contrast, arsenic did not affect degradation or growth, even at very high concentrations of 100 mg/L. Subsequent analyses additionally revealed that concentrations of arsenic remained unchanged following incubation, while those of cadmium and copper decreased significantly.

• Clinical and Experimental Pediatrics
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• v.58 no.11
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• pp.407-414
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• 2015

Early-onset epileptic encephalopathies are one of the most severe early onset epilepsies that can lead to progressive psychomotor impairment. These syndromes result from identifiable primary causes, such as structural, neurodegenerative, metabolic, or genetic defects, and an increasing number of novel genetic causes continue to be uncovered. A typical diagnostic approach includes documentation of anamnesis, determination of seizure semiology, electroencephalography, and neuroimaging. If primary biochemical investigations exclude precipitating conditions, a trial with the administration of a vitaminic compound (pyridoxine, pyridoxal-5-phosphate, or folinic acid) can then be initiated regardless of presumptive seizure causes. Patients with unclear etiologies should be considered for a further workup, which should include an evaluation for inherited metabolic defects and genetic analyses. Targeted next-generation sequencing panels showed a high diagnostic yield in patients with epileptic encephalopathy. Mutations associated with the emergence of epileptic encephalopathies can be identified in a targeted fashion by sequencing the most likely candidate genes. Next-generation sequencing technologies offer hope to a large number of patients with cryptogenic encephalopathies and will eventually lead to new therapeutic strategies and more favorable long-term outcomes.