Medicinal Chemistry : Article ; A Series of Novel Terpyridine-Skeleton Molecule Derivants Inhibit Tumor Growth and Metastasis by Targeting Topoisomerases

( Han Byeol Kwon ),( Chan Mi Park ),( Kyung Hwa Jeon ),( Eun Young Lee ),( Song Eun Park ),( Kyu Yeon Jun ),( Tara Man Kadayat ),( Pritam Thapa ),( Radha Karki ),( Young Hwa Na ),( Mi Sun Park ),( Seu 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

A series of novel terpyridine-skeleton molecules containing conformational rigidity, 14 containing benzo[4,5]-furo[3,2,-ь]pyridine core and 15 comprising chromeno[4,3-ь]pyridine core, were synthesized, and their biological activities were evaluated. 3-(4-phenylbenzo[4,5]furo[3,2-ь]pyridin-2-yl)phenol (8) was determined to be a nonintercalative topo I and II dual catalytic inhibitor and 3-(4-phenylchromeno[4,3-ь]pyridine-2yl)phenol (22) was determined to be a non-intercalative tope IIa specific catalytic inhibitor by various assays. These two catalytic inhibitors induced apoptosis in addition to G1 arrest in T47D human breast cancer cells with much less DNA toxicity than etoposide. Compounds 8 and 22 significantly inhibited tumor growth in HCT15 subcutaneously implanted xenografted mice. The modification of compounds 8 and 22 with the introduction of a methoxy instead of a hydroxy group enhanced endogenous topo inhibitory activity, metabolic stability in diverse types of liver microsomes and improved pharmacokinetic parameters in rat plasma such as augmentation of bioavailability (41.3% and 33.2% for 2-(3-methoxyphenly)-4-4phenylbenzofuro[ 3,2,] pyridine (8-M) and 3-(4-phenylchromeno-[4,3-ь]pyridine-2-yl)methoxybenzene (22-M), respectively).

A Series of Novel Terpyridine-Skeleton Molecule Derivants Inhibit Tumor Growth and Metastasis by Targeting Topoisomerases

Kwon, Han-Byeol,Park, Chanmi,Jeon, Kyung-Hwa,Lee, Eunyoung,Park, So-Eun,Jun, Kyu-Yeon,Kadayat, Tara Man,Thapa, Pritam,Karki, Radha,Na, Younghwa,Park, Mi Sun,Rho, Seung Bae,Lee, Eung-Seok,Kwon, Youngjo American Chemical Society 2015 Journal of medicinal chemistry Vol.58 No.3

<P>A series of novel terpyridine-skeleton molecules containing conformational rigidity, 14 containing benzo[4,5]furo[3,2-<I>b</I>]pyridine core and 15 comprising chromeno[4,3-<I>b</I>]pyridine core, were synthesized, and their biological activities were evaluated. 3-(4-Phenylbenzo[4,5]furo[3,2-<I>b</I>]pyridin-2-yl)phenol (<B>8</B>) was determined to be a nonintercalative topo I and II dual catalytic inhibitor and 3-(4-phenylchromeno[4,3-<I>b</I>]pyridine-2-yl)phenol (<B>22</B>) was determined to be a nonintercalative topo IIα specific catalytic inhibitor by various assays. These two catalytic inhibitors induced apoptosis in addition to G1 arrest in T47D human breast cancer cells with much less DNA toxicity than etoposide. Compounds <B>8</B> and <B>22</B> significantly inhibited tumor growth in HCT15 subcutaneously implanted xenografted mice. The modification of compounds <B>8</B> and <B>22</B> with the introduction of a methoxy instead of a hydroxy group enhanced endogenous topo inhibitory activity, metabolic stability in diverse types of liver microsomes and improved pharmacokinetic parameters in rat plasma such as augmentation of bioavailability (41.3% and 33.2% for 2-(3-methoxyphenyl)-4-phenylbenzofuro[3,2-<I>b</I>]pyridine (<B>8-M</B>) and 3-(4-phenylchromeno[4,3-<I>b</I>]pyridine-2-yl)methoxybenzene (<B>22-M</B>), respectively).</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2015/jmcmar.2015.58.issue-3/jm501023q/production/images/medium/jm-2014-01023q_0017.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm501023q'>ACS Electronic Supporting Info</A></P>

A large-scale screening analysis for the evaluation of Bakanae disease in rice

Myung-Hee Kim,Saet-Byeol Lee,Tackmin Kwon,Un-Ha Hwang,Soo-Kwon Park,Yeong-Nam Youn,Jong-Hee Lee,Jun-Hyun Cho,Dongjin Shin,Sang-Ik Han,Un-Sang Yeo,You-Chun Song,Min-Hee Nam,Dong-Soo Park 한국육종학회 2013 한국육종학회 심포지엄 Vol.2013 No.07

Bakanae disease of rice, caused by Fusarium moniliforme Sheldon, the imperfect stage of Gibberella fujikuroi, is one of the most important rice diseases worldwide, but no rice variety has been found to be completely resistant to this fungus. Cultivation of resistant cultivars is the most beneficial way of reducing quantitative or qualitative losses to for bakanae disease in rice. To facilitate the study of this disease, accurate and large scale screening methods were developed for the inoculation and evaluation of Bakanae disease. Even and large scale infection was achieved by using F. moniliforme spore in tissue embedding cassette and seedling tray. The efficiency of F. moniliforme infection with the concentration of 1×106 spore/ml caused better distribution (F-value=33.96) than 1×102 (F-value=10.69), and 1×104 spore/ml (F-value=2.63). We established new criteria of healthy and non-healthy plant, and introduced calculation of proportion of healthy plants to meet fast evaluation of resistance level of each variety. The effect of F. moniliforme strains containing different genetic background was also evaluated with rice varieties to figure out the stability of resistance level. GA3 response of rice variety was significantly correlated with bakanae disease, but it did not adequate for direct indicator of bakanae disease resistance. These results indicated that a large scale infection method developed in this study is fast and reproducible, as well as a disease evaluation system provides an accurate measurement of bakanae disease resistance of rice.

Quantitative computed tomographic evaluation of bone mineral density in beagle dogs: comparison with dual-energy x-ray absorptiometry as a gold standard

KWON, Danbee,KIM, Jaehwan,LEE, Hyeeun,KIM, Byeol,HAN, HyunHee,OH, HyunJu,KIM, MinJung,YOON, Hakyoung,LEE, ByeongChun,EOM, Kidong The Japanese Society of Veterinary Science 2018 The Journal of veterinary medical science Vol.80 No.4

<P>This study aimed to demonstrate the higher accuracy and reproducibility of quantitative computed tomography (QCT) compared with dual-energy X-ray absorptiometry (DXA) as a gold standard for measuring canine bone mineral density (BMD). Seven middle-aged beagle dogs underwent lumbar vertebral and bilateral femoral DXA and QCT scans. BMD (mg/cm<SUP>2</SUP>) was measured at the vertebral body from L2 to L6, femoral neck, and proximal and distal femoral diaphyses. The BMD values were measured 3 times and compared. The BMD value on QCT was higher than that on DXA for femoral BMD but not for vertebral BMD. The correlation was strong for the lumbar vertebrae (r=0.66) and was strongest for L3 (r=0.85). No correlation was found for the femoral neck (<I>P</I>=0.35), and only moderate correlations were found for the proximal and distal femoral diaphyses (r=0.43 and r=0.40, respectively). The limits of agreement were narrower for vertebral BMD than for femoral BMD, and L3 had the narrowest limits of agreement. The intraclass correlation (ICC) was higher for DXA than for QCT at all lumbar and femoral sites measured, but the ICC of QCT was higher than 0.7. In conclusion, L3 can be used to monitor changes in BMD, and relative values and sequential monitoring of femoral BMD can also be useful because of the high reproducibility of QCT measurements. QCT would be a useful technique for evaluation of BMD in veterinary practice.</P>

Direct Conversion of Adult Skin Fibroblasts to Endothelial Cells by Defined Factors

Han, Jung-Kyu,Chang, Sung-Hwan,Cho, Hyun-Ju,Choi, Saet-Byeol,Ahn, Hyo-Suk,Lee, Jaewon,Jeong, Heewon,Youn, Seock-Won,Lee, Ho-Jae,Kwon, Yoo-Wook,Cho, Hyun-Jai,Oh, Byung-Hee,Oettgen, Peter,Park, Young-Ba American Heart Association 2014 Circulation Vol.130 No.14

<P><B>Background—</B></P><P>Cell-based therapies to augment endothelial cells (ECs) hold great therapeutic promise. Here, we report a novel approach to generate functional ECs directly from adult fibroblasts.</P><P><B>Methods and Results—</B></P><P>Eleven candidate genes that are key regulators of endothelial development were selected. Green fluorescent protein (GFP)–negative skin fibroblasts were prepared from Tie2-GFP mice and infected with lentiviruses allowing simultaneous overexpression of all 11 factors. Tie2-GFP<SUP>+</SUP> cells (0.9%), representing Tie2 gene activation, were detected by flow cytometry. Serial stepwise screening revealed 5 key factors (Foxo1, Er71, Klf2, Tal1, and Lmo2) that were required for efficient reprogramming of skin fibroblasts into Tie2-GFP<SUP>+</SUP> cells (4%). This reprogramming strategy did not involve pluripotency induction because neither Oct4 nor Nanog was expressed after 5 key factor transduction. Tie2-GFP<SUP>+</SUP> cells were isolated using fluorescence-activated cell sorting and designated as induced ECs (iECs). iECs exhibited endothelium-like cobblestone morphology and expressed EC molecular markers. iECs possessed endothelial functions such as <I>Bandeiraea simplicifolia</I>-1 lectin binding, acetylated low-density lipoprotein uptake, capillary formation on Matrigel, and nitric oxide production. The epigenetic profile of iECs was similar to that of authentic ECs because the promoters of VE-cadherin and Tie2 genes were demethylated. mRNA profiling showed clustering of iECs with authentic ECs and highly enriched endothelial genes in iECs. In a murine model of hind-limb ischemia, iEC implantation increased capillary density and enhanced limb perfusion, demonstrating the in vivo viability and functionality of iECs.</P><P><B>Conclusions—</B></P><P>We demonstrated the first direct conversion of adult fibroblasts to functional ECs. These results suggest a novel therapeutic modality for cell therapy in ischemic vascular disease.</P>

Whitening Effects of Aerial Part of Pueraria Thunbergiana in vitro and in vivo

Eun Byeol Han(한은별),Bo Yoon Chang(장보윤),Svay Thida(디다스와이),Dae Sung Kim(김대성),Hyoung Kwon Cho(조형권),Sung Yeon Kim(김성연) 환경독성보건학회 2013 한국독성학회 심포지움 및 학술발표회 Vol.2013 No.10

Solvothermal liquefaction of lignin from oil palm empty fruit bunches in a bench-scale continuous stirred tank reactor

Ivan KRISTIANTO,Han Byeol KIM,Cheol Woo PARK,Young-Kwon PARK,Jungho JAE 대한환경공학회 2019 대한환경공학회 학술발표논문집 Vol.2019 No.-

원산지별 감초 추출물의 항산화 활성 비교 연구

한샛별 ( Saet Byeol Han ),구현아 ( Hyun A Gu ),김수지 ( Su Ji Kim ),김혜진 ( Hye Jin Kim ),권순식 ( Soon Sik Kwon ),김해수 ( Hae Soo Kim ),전소하 ( So Ha Jeon ),황준필 ( Jun Pil Hwang ),박수남 ( Soo Nam Park ) 대한화장품학회 2013 대한화장품학회지 Vol.39 No.1

본 연구에서는 한국과 중국 감초(Glycyrrhiza uralensis) 및 우즈베키스탄 감초(Glycyrrhiza glabra)를 이용하여 원산지별 감초 추출물의 항산화 활성에 관한 비교 연구를 수행하였다. 감초 추출물의 자유 라디칼(1, 1-phenyl-2-picrylhydrazyl, DPPH) 소거활성(FSC₅₀)은 각 3가지 원산지 중 한국 감초가 50% 에탄올 추출물(21.15 μg/mL), 에틸아세테이트 분획(29.15 μg/mL), 아글리콘 분획(3.26 μg/mL)에서 모두 가장 우수한 활성을 나타내었다. 루미놀-의존성 화학발광법을 이용한 Fe³⁺-EDTA/H₂O₂ 계에서 생성된 활성산소종(reactive oxygen species, ROS)에 대한 감초 추출물의 총 항산화능(OSC₅₀)은 중국 감초의 50% 에탄올 추출물(1.00 μg/mL)과 에틸아세테이트 분획(0.34μg/mL)이 가장 높은 활성을 나타내었다. Rose-bengal로 증감된 사람 적혈구의 광용혈에 대한 억제 효과를 측정하였을 때 원산지별 감초의 50% 에탄올 추출물과 아글리콘 분획 모두 농도범위(5 ~ 50 μg/mL)에서 농도의존적으로 세포 보호 효과를 나타내었으며, 특히 아글리콘 분획(10 μg/mL)의 경우 한국 감초(τ₅₀ = 847.4 min)가 동일한 종인 중국 감초(τ₅₀ = 194.3 min)보다 약 4배 더 우수한 활성을 나타내었다. 이상의 결과를 통해 미백 소재로만 주로 사용되어오던 감초 추출물이 천연 항산화제로서 화장품 분야에 응용될 수 있을 것으로 예상된다. 특히 세포 보호 효과가 우수한 것으로 보아 감초 추출물이 자외선으로 유도된 ¹O₂와 외 ROS로부터 피부를 효과적으로 보호할 수 있을 것으로 예상된다. In this work, comparative study on antioxidative activities of extracts from Glycyrrhiza uralensis (G. uralensis) produced in Korea and in China and Glycyrrhiza glabra (G. glabra) produced in Uzbekistan was conducted. Among three origins, 50% ethanol extracts (21.15 μg/mL), ethyl acetate fraction (29.15 μg/mL) and aglycone fraction (3.26 μg/mL) of G. uralensis from Korea showed the higher free radical (1,1-phenyl-2-picrylhydrazyl, DPPH) scavenging activity (FSC₅₀) than extracts from other origins. Reactive oxygen species (ROS) scavenging activities (OSC₅₀) of extracts from three origins on ROS generated in Fe³⁺-EDTA/H₂O₂ system were investigated using luminol-dependent chemiluminescence assay 50% ethanol extract (1.00 μg/mL) and ethyl acetate fraction (0.34 μg/mL) of G. uralensis from China showed the most prominent ROS scavenging activity. The protective effects of extract/fractions of G. uralensis and G. glabra extracts on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. 50% ethanol extract and aglycone fraction of G. uralensis and G. glabra extracts from three origins showed cellular protective effects in a concentration dependent manner (5 ∼ 50 μg/mL). Aglycone fraction of G. uralensis from Korea (τ₅₀ = 847.4 min)especially showed cellular protective effects four times higher than that from China (τ₅₀ = 194.3 min). These results indicate that G. uralensis and G. glabra extracts, which have been used as whitening agent, could be applicable to functional cosmetic ingredient as a natural antioxidant. Judging from the prominent cellular protecitve effects, it is concluded that G. uralensis and G. glabra extracts can protect the skin from ¹O₂ and various ROS induced by UV.

미성숙 복분자 과실의 항산화 효능 및 타이로시네이즈 저해 활성 평가

한샛별 ( Saet Byeol Han ),권순식 ( Soon Sik Kwon ),공봉주 ( Bong Ju Kong ),김경진 ( Kyeong Jin Kim ),박수남 ( Soo Nam Park ) 대한화장품학회 2013 대한화장품학회지 Vol.39 No.4

본 연구에서는 미성숙 복분자 추출물의 항산화 효능과 타이로시네이즈 저해 활성을 평가하고 이들의 기능성 화장품 원료로서의 응용 가능성을 확인하였다. 모든 실험은 미성숙 복분자의 50% 에탄올 추출물, 에틸아세테이트 분획, 아글리콘 분획을 이용하여 진행하였다. DPPH (1,1-diphenyl-2-picrylhydrazyl)법을 이용한 자유 라디칼 소거 활성(FSC₅₀)은 에탄올 추출물(6.56 μg/mL)과 에틸아세테이트 분획(6.14 μg/mL)이 대표적인 지용성 항산화제인 (+)-α-tocopherol (8.98 μg/mL)보다 높은 것으로 나타났다. Fe³⁺-EDTA/H₂O₂계에서 생성된 활성산소종에 대한 소거 활성(OSC₅₀)은 에탄올 추출물(0.83 μg/mL), 에틸아세테이트 분획(0.84 μg/mL), 아글리콘 분획(1.13 μg/mL) 세 분획 모두 대표적인 수용성 항산화제인 L-ascorbic acid(1.5 μg/mL)보다 높은 것으로 나타났다. Rose bengal로 광증감된 ¹O₂에 의한 적혈구 파괴에 대하여, 세 분획 모두 농도 의존적(1 ~ 50 μg/mL)인 세포보호 활성을 나타내었다. 또한 50 μg/mL 농도를 기준으로 비교하였을 때, 50% 에탄올 추출물의 τ₅₀은 296.3 min으로 가장 높은 세포보호 활성을 나타내었다. 타이로시네이즈 저해 활성에서 에틸아세테이트 분획과 아글리콘 분획은 알부틴보다 높은 저해 효과를 나타내었다. 이상의 결과들로부터 미성숙 복분자 추출물은 라디칼을 포함한 활성산소종을 소거하는 항산화제로서, 알부틴을 대체하는 미백 기능성 원료로서 응용될 수 있음을 확인하였다. In this study, the antioxidative effects and inhibitory activities of unripened fruit extract of Rubus coreanus Miquel (R. coreanus Miquel) on tyrosinase were investigated and the potential applicability as a cosmeceutical ingredients was evaluated. All experiments were performed with 50% ethanol extract, ethyl acetate fraction and aglycone fraction of unripened fruit extract of R. coreanus Miquel. The DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activites (FSC₅₀) of 50% ethanol extract (6.56 μg/mL) and ethyl acetate fraction (6.14 μg/mL) of unripened fruit extract of R. coreanus Miquel were higher than (+)-α-tocopherol (8.98 μg/mL), which is known as a typical hydrophobic antioxidant. Reactive oxygen species (ROS) scavenging activities (OSC₅₀) of 50% ethanol extract (0.83 μg/mL), ethyl acetate fraction (0.84 μg/mL) and aglycone fraction (1.13 μg/mL) of R. coreanus Miquel on ROS generated in Fe³⁺ -EDTA/H₂O₂ system were higher than L-ascorbic acid (1.5 μg/mL), which is known as s typical hydrophilic antioxidant. The cellular protective effect of extract and fraction of unripened fruit extract of R. coreanus Miquel on the rose bengal sensitized photohemolysis of human erythrocytes was increased in a concentration dependent manner (1 ~ 50 μg/mL). And 50% ethanol extract in 50 μg/mL showed the most protective effect among extracts (τ₅₀ = 296.3 min). The inhibitory effects on tyrosinase of ethyl acetate and agylcone fractions were higher than arbutin. These results indicate that unripened fruit extracts of R. coreanus Miquel can be applied to antioxidant scavenging ROS including radical as an alternative whitening agent to replace arbutin.

The solubilization method of human interferon β produced by recombinant Escherichia coli.

Da-Jin SON,Saet-Byeol KIM,Jong-Seok KIM,Deok-ho KWON,Jae-bum PARK,Young-Jun CHANG,Hyung-Moo JUNG,Sang-In HAN,Eock-Kee HONG,Suk-Jin HA 한국생물공학회 2017 한국생물공학회 학술대회 Vol.2017 No.10