• Archives of Pharmacal Research
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• 제28권2호
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• pp.159-163
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• 2005

The effects of sedative peptide alkaloids from Zizyphus species on calmodulin- dependent protein kinase II were investigated. Protein kinase II activity was assayed on the basis of its ability to activate tryptophan 5-monooxygenase as its substrate in the presence of calmodulin. All thirteen alkaloids tested were stronger inhibitors than chlorpromazine ($IC_50,\;98{\mu}M$) on calmodulin-dependent protein kinase II. Among them, the most potent inhibitor was daechuine S27 ($IC_{50},\;2.95{\mu}M$), which was stronger than pimozide ($IC_{50},\;15.0{\mu}M$).

• 통합자연과학논문집
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• 제5권2호
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• pp.72-78
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• 2012

Multidrug resistance is a major obstacle in cancer chemotherapy. Cancer cells efflux chemotherapeutic drug out of cell by means of transporter and reduce the active concentration of it inside cell. Such transporters are member of the ATP binding cassettes (ABC) protein. It includes P-gp, multiple resistant protein (MRP), and breast cancer resistant protein (BCRP). These proteins are widely distributed in the human cells such as kidney, lung, endothelial cells of blood brain barrier etc. However, there are number of drugs developed for it, but most of them are getting transported by it. So, still there is necessity of a good modulator, which could effectively combat the transport of chemotherapeutic agents. Natural products origin modulators were found to be effective against transporter such as flavonoids, which belongs to third generation modulators. They have advantage over synthetic inhibitor in the sense that they have simple structure and abundant in nature. This review focuses on the P-gp structure its architecture, efflux mechanism, herbal inhibitors and their mechanism of action.

• Animal cells and systems
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• 제2권2호
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• pp.233-238
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• 1998

Certain basic characteristics of choline uptake in nerve terminals were studied with synaptosomes from rat hippocampus. Synaptosomal $[^3H]$-choline uptake was clarified as specific and high affinity by low Km value(2.2 uM), Na+-dependency and high sensitivity to hemicholinium-3, a competitive inhibitor of choline uptake. Choline uptake into synaptosomes was linearlys related to Na+ concentration and membrane potential. Extracellular Ca2+ modulated the choline uptake, but probably not through increase of intracellular $Ca^{2+}$, because this modulation was not affected the by high $K^+$-depolarization. EGTA (2mM) added for $Ca^{2+}$-free condition had a peculiar effect of decreasing choline uptake. These results suggest that Ca2+ may play an important role in regulating the metabolism of acetylcholine in the nerve terminals directly through the increase of acetylcholine release.

• 통합자연과학논문집
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• 제9권1호
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• pp.41-61
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• 2016

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Phosphoinositide 3-kinases (PI3Ks) play important role in Non-Small Cell Lung Cancer. PI3Ks constitute a lipid kinase family which modulates the function of numerous substrates involved in the regulation of cell survival, cell cycle progression and cellular growth. Herein, we describe the ligand based pharmacophore combined with molecular docking studies methods to identify new potent PI3K inhibitors. Several pharmacophore models were generated and validated by Guner-Henry scoring Method. The best models were utilized as 3D pharmacophore query to screen against ZINC database (Chemical and Natural) and the retrieved hits were further validated by fitness score, Lipinski's rule of five. Finally four compounds were found to have good potential and they may act as novel lead compounds for PI3K inhibitor designing.

• 약학회지
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• 제41권4호
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• pp.456-461
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• 1997

Tyrosinase is known to accelerate the melanin polymer biosynthesis in melanocyte, so tyrosinase inhibitors hinder the melanin polymer biosynthesis and are useful not only for th e material used in cosmetics as skin-whitening agents but also as the remedy for disturbances in pigmentation. During our search for new melanin biosynthesis inhibitors from natural sources, 130 higher plants were tested for the inhibitory effect against tyrosinase activity by the mushroom tyrosinase assay. Among them, Carex humilis ($IC_{50}$, 10vg/ml), Sophora flavescence ($IC_{50},\;20{\sim}50{mu}g/ml$) and Styrax japonica ($IC_{50},\;10{\mu}g/ml$) inhibited the tyrosinase activity strongly.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.344.2-344.2
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• 2002

Sophoricoside analogs are natural isoflavonoids isolated from fruits of Sophora japonica L. and exhibited an inhibitory effect on IL -5. Many synthetic variations on isoflavonoids has been reported. but relatively few examples of quinolone analogs have been described. As part of our endeavor to develop novel and effective IL-5 inhibitor, we have synthesized azaisoflavones by cyclization of the key intermediate, 2'-aminochalocone obtained from substituted aniline. The synthesized azaisoflavones were evaluated for their inhibitory activtities on IL-5 comparing with natural Sophoricoside analogs. None of the azaisoflavones showed promixing inhibitory effects In the assay. Nevertheless. assay data Indicated that 5.7-phenolic hycroxy groups on the A-ring and alkyl subsitiuent on N1 seemed to play an importnt role in the IL-5 bioassay.

• 동의생리병리학회지
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• 제18권5호
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• pp.1505-1511
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• 2004

Inhibition of angiotensin converting enzyme (ACE) activity is one of the common antihypertensive methods functioned by drugs such as captopril, lisinopril and enalapril to serve as inhibitors of ACE. This study was designed to compare the effects of enalapril, an angiotensin-converting enzyme inhibitor and GLM002, an oriental medicine, on tail systolic pressure, aorta and plasma properties in spontaneously hypertensive rats (SHR) after 4 weeks of treatment. During the treatment, blood pressure was depressed to normal in GLM002 and enalapril groups. The treatments of enalapril and GLM002 were discontinued in 4 weeks. One week after the treatment stop, systolic blood pressure was smoothly increased in both groups; the increment of blood pressure was slightly greater in GLM002-SHR, but the increment of plasma ACE activity was proportionately similar in each group. In the aspects of the triglyceride, HDL and total cholesterol level, those levels were slightly different among each group. We also conducted clinical dosage of GLM002 to the patients who have mild and severe hypertension for approximately 7 weeks. Clinical treatments also showed remarkable efficiencies on blood pressure (systolic blood pressure, diastolic blood pressure), complete blood count (CBC) routine, differ count (NEUTRO, LYM, MONO, EOS and BASO) and R-chemistry. We conclude that GLM002, like already proven enalapril, plays a role as an angiotensin-converting enzyme inhibitor, and can be suggested as a drug candidate for curing hypertension.

• Journal of Microbiology and Biotechnology
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• 제30권1호
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• pp.31-37
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• 2020

We previously identified a new heparinase inhibitor fungal metabolite, named CRM646-A, which showed inhibition of heparinase and telomerase activities in an in vitro enzyme assay and antimetastatic activity in a cell-based assay. In this study, we elucidated the mechanism by which CRM646-A rapidly induced nucleus condensation, plasma membrane disruption and morphological changes by increasing intracellular Ca²⁺ levels. Furthermore, PD98059, a mitogen-activated protein kinase (MEK) inhibitor, inhibited CRM646-A-induced nucleus condensation through ERK1/2 activation in rat 3Y1 fibroblast cells. We identified CRM646-A as a Ca²⁺ ionophore-like agent with a distinctly different chemical structure from that of previously reported Ca²⁺ ionophores. These results indicate that CRM646-A has the potential to be used as a new and effective antimetastatic drug.

• 한국약용작물학회지
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• 제15권2호
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• pp.89-94
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• 2007

The effects of angiogenesis inhibitor from the extract libraries of Korean and Chinese medicinal plants were investigated using a protein microarray chip. Protein chip was constructed by immobilization of integrin ${\alpha}_5{\beta}_1$ on protein chip base plates and employed far screening active extracts that inhibit the integrin-fibronectin interaction from the extract libraries. The 100 extracts of medicinal plants were obtained from extract bank of National Institute of Crop Science, RDA. The 14 extracts among 100 extract libraries were shown efficient inhibition activity for the interaction between integrin-fibronectin. The medicinal plants of 14 extracts were Vitex negundo var. incisa (Lam.) C.B. Clarke, Epimedium koreanum Nakai, Cedrela sinensis A. Juss, Ipomea aquatica Forsk, Schisandra chinensis Baill, Pulsatilla koreana Nakai, Paeonia lactiflora Pall. var.hortensis Makino, Oenothera odorata, Allium chinense, Allium victorialis var. platyphyllum MAKINO, Polygonatum odoratum Druce var. pluriflorum Ohwi, Hosta lancifolia, Agrimonia pilosa L. var. japonica Nakai and Potentilla chinensis SER. The Paeonia lactiflora, Oenothera, and Agrimonia pilosa from these 14 extracts libraries were shown strong inhibition activity of integrin ${\alpha}_5{\beta}_1$.

• BMB Reports
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• 제36권2호
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• pp.223-229
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• 2003

The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.