• Proceedings of the PSK Conference
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• 2003.10a
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• pp.93-93
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• 2003

RNA plays an important role in numerous biological processes but little is known about the interactions between small organic molecules and RNA. Our previous work has shown that the heterodimeric compound designed by conjugation with neomycin and loop-specific chemical bind to the stem-loop structured RNA motifs. In the present study, heterodimer was used, in a reverse way, as a probe to identify structured RNA motifs. (omitted)

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.246.2-246.2
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• 2001

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.275-282
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• 2015

In the present study, we synthesized a series of novel 7-methoxy-N-(substituted phenyl)benzofuran-2-carboxamide derivatives in moderate to good yields and evaluated their neuroprotective and antioxidant activities using primary cultured rat cortical neuronal cells and in vitro cell-free bioassays. Based on our primary screening data with eighteen synthesized derivatives, nine compounds (1a, 1c, 1f, 1i, 1j, 1l, 1p, 1q and 1r) exhibiting considerable protection against the NMDA-induced excitotoxic neuronal cell damage at the concentration of $100{\mu}M$ were selected for further evaluation. Among the selected derivatives, compound 1f (with $-CH_3$ substitution at R2 position) exhibited the most potent and efficacious neuroprotective action against the NMDA-induced excitotoxicity. Its neuroprotective effect was almost comparable to that of memantine, a well-known NMDA antagonist, at $30{\mu}M$ concentration. In addition to 1f, compound 1j (with -OH substitution at R3 position) also showed marked anti-excitotoxic effects at both 100 and $300{\mu}M$ concentrations. These findings suggest that $-CH_3$ substitution at R2 position and, to a lesser degree, -OH substitution at R3 position may be important for exhibiting neuroprotective action against excitotoxic damage. Compound 1j was also found to scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit in vitro lipid peroxidation in rat brain homogenate in moderate and appreciable degrees. Taken together, our structure-activity relationship studies suggest that the compound with $-CH_3$ substitution at R2 and -OH substitution at R3 positions of the benzofuran moiety might serve as the lead exhibiting potent anti-excitotoxic, ROS scavenging, and antioxidant activities. Further synthesis and evaluation will be necessary to confirm this possibility.

• Animal cells and systems
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• v.12 no.1
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• pp.11-14
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• 2008

Finding a way to strengthen human cognitive functions, such as learning and memory, has been of great concern since the moment people realized that these functions can be affected and even altered by certain chemicals. Since then, plenty of endeavors have been made to look for safe ways of improving cognitive performances without adverse side-effects. Unfortunately, most of these efforts have turned out to be unsuccessful until now. In this study, we examine the effect of a natural compound, idesolide, on hippocampus-dependent recognition memory. We demonstrate that idesolide is effective in the enhancement of recognition memory, as measured by a novel object recognition task. Thus, idesolide might serve as a novel therapeutic medication for the treatment of memoryrelated brain anomalies such as mild cognitive impairment(MCI) and Alzheimer's disease.

• Journal of Genetic Medicine
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• v.14 no.2
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• pp.80-85
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• 2017

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder characterized by an abnormal accumulation of methylmalonyl-CoA and methylmalonate in body fluids without hyperhomocysteinemia. Cardiac disease is a rarely known lethal complication of MMA, herein, we report a Korean neonate diagnosed with MMA on the basis of biochemical and genetic findings, who developed cardiomyopathy, resulting in sudden death. The patient presented vomiting and lethargy at 3 days of age. Initially, the patient had an increased plasma propionylcarnitine/acetylcarnitine concentration ratio of 0.49 in a tandem mass spectrometry analysis and an elevated ammonia level of $537{\mu}mol/L$. Urine organic acid analysis showed increased excretion of methylmalonate. Subsequent sequence analysis of the methylmalonyl-CoA mutase (MUT) gene revealed compound heterozygous mutations c.323G>A (p.Arg108His) in exon 1 and c.1033_1034del (p. Leu345Serfs*15) in exon 4, the latter being a novel mutation. In summary, this is the first case of MMA and cardiomyopathy in Korea that was confirmed by genetic analysis to involve a novel MUT mutation.

• ETRI Journal
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• v.34 no.5
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• pp.743-752
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• 2012

Semantic interpretation of the relationship between noun compound (NC) elements has been a challenging issue due to the lack of contextual information, the unbounded number of combinations, and the absence of a universally accepted system for the categorization. The current models require a huge corpus of data to extract contextual information, which limits their usage in many situations. In this paper, a new semantic relations interpreter for NCs based on novel lightweight binary features is proposed. Some of the binary features used are novel. In addition, the interpreter uses a new feature selection method. By developing these new features and techniques, the proposed method removes the need for any huge corpuses. Implementing this method using a modular and plugin-based framework, and by training it using the largest and the most current fine-grained data set, shows that the accuracy is better than that of previously reported upon methods that utilize large corpuses. This improvement in accuracy and the provision of superior efficiency is achieved not only by improving the old features with such techniques as semantic scattering and sense collocation, but also by using various novel features and classifier max entropy. That the accuracy of the max entropy classifier is higher compared to that of other classifiers, such as a support vector machine, a Na$\ddot{i}$ve Bayes, and a decision tree, is also shown.

• Archives of Pharmacal Research
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• v.22 no.5
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• pp.491-495
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• 1999

In order to examine the effects of N-substituted alkyl group on the anticonvulsant activities of N-Cbz-$\alpha$-aminoglutarimides as novel anticonvulsants with broad spectrum, a series of (R) or (S) N-Cbz-$\alpha$-amino-N-alkylglutarimides (1 and 2) were prepared from the corresponding (R) or (S) N-Cbz-glutamic acid and evaluated for the anticonvulsant activities in the maximal electroshock seizure (MES) test and pentylenetetrazol induced seizure(PTZ) test, including the neurotoxicity. The most potent compound in the MES test was (S) N-Cbz-$\alpha$-amino-N-methylglutarimide($ED_{50}$=36.3 mg/kg, PI=1.7). This compound was also most potent in the PTZ test ($ED_{50}$=12.5 mg/kg, PI=5.0). The order of anticonvulsant activities against the MES test as evaluated form $ED_{50}$ values for (R) series was N-methyl > N-H > N-ethyl > N-allyl ; for the (S) series N-methyl > N-H > N-ethyl > N-alkyl > N-isobutyl compound. Against the PTZ tests, the order of anticonvulsant activities showed similar pattern ; for the (R) series, N-methyl > N-H > N-ethyl > N-allyl ; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. From the above results, N-substituted alkyl groups were though to play an important role for the anticonvulsant activities of N-Cbz-$\alpha$-amino-N-alkylgutarimides.

• Journal of Korean Neurosurgical Society
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• v.65 no.1
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• pp.4-12
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• 2022

Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.191-202
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• 2022

Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D₂ receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D₂ receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.