Potential Antitumor $\alpha$-Methylene-$\gamma$-butyrolactone-Bearing Nucleic Acid Base. 3. Synthesis of $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans

Kim, Jack-C.,Kim, Si-Hwan,Kim, Ji-A,Choi, Soon-Kyu,Park, Won-Woo The Pharmaceutical Society of Korea 1998 Archives of Pharmacal Research Vol.21 No.4

Search for a new $\alpha$-methylene-$\gamma$-butyrolactone-bearing 6-substituted purine as a potental antitumor agent has led to synthesize seven, hitherto unreported, $5^1$-Methyl-$5^1$-[(6-substituted-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$- methylenetetrahydrofurans (H, Cl, l, $CH_3$, $NH_2$, SH, >C=O) (6a-g). These include $5^1$-Methyl-$5^1$-[(9H-purin-9-yl)methyll-$2^1$-oxo-$3^1$ -methylenetetrahydrofurans (6a), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydr ofurans (6b), $5^1$-Methyl-$5^1$-[(6-chloro-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6c), $5^1$-Methyl-$5^1$-[(6-methyl-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6d), $5^1$-Methyl-$5^1$-[(9H-adenin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6e), $5^1$-Methyl-$5^1$-[(6-mercapto-9H-purin-9-yl) methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofurans (6f) and $5^1$-Methyl-$5^1$-[(9H-hypoxanthin-9-yl)methyll-$2^1$-oxo-$3^1$-methylenetetrahydrof urans (6g) which were made by the Reformatsky-type reaction of ethyl $\alpha$-(bromomethyl) acrylate with the corresponding (6-substituted-9H-purin-9-yl)-2-propanone intermediates (5a-g). These ketone intermediates 5a-g, 1-(9H-purin-9-yl)-2-propanone (5a), 1-(6-chloro-9H-purin-9-yl)-2-propanone (5b), 1-(6-iodo-9H-purin-9-yi)-2-propanone (5c), 1-(6-methyl-9H-purin-9-yl)-2-propanone (5d), 1-(9H-adenin-9-yl)-2-propanone (Se), 1-(6-mercapto-9H-purin-9-yl)-2-propanone (5f), and 1-(9H-hypoxanthin-9-yl)-2-propanone (5g) were directly obtained by the alkylation of the 6-substituted purine bases with the chloroacetone in the presence of $K_2$$CO_3$ (or NaH) under DMF (or DMSO). The preliminary in vitro cytotoxcity assay for the synthetic .alpha.-methylene-y-butyro-lactone compounds (6a-g) were determined against three cell lines (PM-3A, P-388, and K-562) and showed the moderate antitumor activity ($IC_50$ ranged from 1.4 to 4.3 $\mu\textrm{g}$/ml) with the compound $5^1$-methyl-$5^1$ -[(9H-hypoxanthin-9-yl)methyl]-$2^1$-oxo-$3^1$-methylenetetrahydrofuran (6g) showing the least antitumor activity.

Tonal development and voice quality in the stops of Seoul Korean

Yu, Hye Jeong 한국음성학회 2018 말소리와 음성과학 Vol.10 No.4

Korean stops are currently undergoing a tonogenetic sound change, as found in the Seoul dialect in which a merged VOT of aspirated and lax stops induces F0 to be the primary cue for distinguishing the two stops and the lax stops have lower F0 than the aspirated stops. In tonal languages, low tone is produced with a breathy voice. This study investigated whether there are changes in voice quality with respect to the tonogenetic sound change of Korean stops. Two age groups speaking the Seoul dialect participated in this study: five females and six males born in the 1940s and 1950s and nine females and eight males born in the 1980s and 1990s. This study replicated previous findings of VOT and F0 and further examined H1-H2, H1-A1, and H1-A2 to see how they correlate with the sound change. In the older and younger generations, H1-H2, H1-A1, and H1-A2 were significantly lower after the tense stops than after the aspirated and lax stops, but they were not significantly different after the aspirated and lax stops. However, the younger females exhibited some different results for H1-H2 and H1-A2 than the older generation. In the younger females, the H1-H2 mean was higher after the aspirated stops than it was after the lax stops at the vowel onset, and the H1-H2 difference increased at the vowel midpoint. Although there was an inter-speaker variation in the results of H1-H2 and H1-A1, analyses of individual speakers showed that the H1-H2 and H1-A1 were higher after the lax stops than after the aspirated stops in the younger female speakers. These results indicate that lax stops tend to be breathier than aspirated stops in the younger female speakers. They also indicate that changes in voice quality are on Korean stops with tonal sound change, but are still developing.

CK2 downregulation induces senescence-associated heterochromatic foci formation through activating SUV39h1 and inactivating G9a

Park, Jeong-Woo,Kim, Jin Joo,Bae, Young-Seuk Elsevier 2018 Biochemical and biophysical research communication Vol.505 No.1

<P><B>Abstract</B></P> <P>Cellular senescence is an irreversible form of cell cycle arrest and senescent cells have a unique gene expression profile that is frequently accompanied by senescence-associated heterochromatic foci (SAHF). Here, we present evidence that CK2 downregulation induces trimethylation of histone H3 Lys 9 (H3K9me3), selective binding of HP1γ to H3K9me3, formation of SAHF, and reduction of cyclin D1 expression in HCT116 and MCF-7 cells. CK2 downregulation-mediated H3K9me3 is associated with induction of H3K9 trimethylase SUV39h1 as well as reduction of H3K9 dimethylase G9a and GLP in cells. In addition, Pharmacological inhibition of SUV39h1 and G9a overexpression significantly attenuated induction of senescence-associated β-galactosidase (SA-β-gal) activity, H3K9me3 and SAHF formation in CK2-downregulated cells. Moreover, CK2 downregulation induced H3K9me3 in nematodes. Taken together, these results demonstrate that CK2 downregulation leads to H3K9me3 and SAHF formation by increasing SUV39h1 and decreasing G9a.</P> <P><B>Highlights</B></P> <P> <UL> <LI> CK2 downregulation induces histone H3K9me3 in human cells and nematodes. </LI> <LI> CK2 downregulation results in induction of SUV39h1 and reduction of G9a and GLP. </LI> <LI> SUV39h1 inhibition or G9a upregulation suppress CK2 knockdown-mediated SAHF formation. </LI> <LI> Therefore, this study suggests that CK2 downregulation induces SAHF formation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Temperature Dependence of the Spin Lattice Relaxation Time of Proton NMR in the Mixed Antiferromagnets A1−xBxCl2·2H2O

Tatsuichi Hamasaki,Kazuko Zenmyo,Hidenori Kubo 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.63 No.3

The mixed transition metal dichloride dihydrates A1−xBxCl2·2H2O (A, B=Co, Mn, Ni) havebeen prepared in order to understand the specificity of the Mn spins in the mixtures. The temperaturedependences of the spin lattice relaxation times T1 of proton nuclear magnetic resonance(NMR) on these mixed crystals have been measured. In Ni1−xBxCl2·2H2O (B=Co, Mn), Mn substitutionincreased the relaxation rates 1/T1 more than Co substitution, even when the amounts ofsubstitution were almost the same. In Co1−xBxCl2·2H2O (B=Mn, Ni), Mn has a significant impacton the relaxation rates in comparison with Ni. In Mn1−xBxCl2·2H2O (B=Ni, Co), the relaxationrates are much increased by a slight substitution of Co and exhibit a minimum in the temperaturerange of observation. This appearance of a minimum in the relaxation rates at low temperatures isbelieved to reflect an instability due to the occurrence of a reentrant spin-glass transition. A similartrend is seen at low temperatures in the case of Ni substitution, too. A Co1−xFexCl2·2H2O (x =0.1) sample has been prepared, too. In this sample, a minimum of the relaxation rate is seen inthe temperature range of observation. This may reflect an instability due to the occurrence of anoblique antiferromagnetic transition.

Synthesis of Novel Benzofuran and Related Benzimidazole Derivatives for Evaluation of In Vitro Anti-HIV-1, Anticancer and Antimicrobial Activities

Samia M. Rida,Soad A. M. El-Hawash,Hesham T. Y. Fahmy,Aly A. Hazzaa,Mostafa M. M. El-Meligy 대한약학회 2006 Archives of Pharmacal Research Vol.29 No.10

Previously, we synthesized and evaluated several benzofuran derivatives containing heterocyclic ring substituents linked to the benzofuran nucleus at C-2 by a two- to four-atom spacer as potential anti-HIV-1, anticancer and antimicrobial agents. Among these derivatives, NSC 725612 and NSC 725716 exhibited interesting anti-HIV-1 activity. To further investigate the structure-activity relationship, we synthesized several new benzofuran derivatives derived from 2-acetylbenzofuran (2, 3a-c) and 2-bromoacetylbenzofuran (6; 7a,b; 8a,b). The compounds were designed to comprise the heterocyclic substituents directly linked to the benzofuran nucleus at C-2. Moreover, various related benzimidazoles derived from 2-acetylbenzimidazole and from 2-cyanomethylbenzimidazole (12a,b; 13a,b; 15; 16a,b) were also prepared as isosteres. The synthesized compounds were preliminarily evaluated for their in vitro anti-HIV-1, anticancer and antimicrobial activity. Compounds 2, 3a, 3b, and 12b showed weak anti-HIV-1 activity. Compound 6 exhibited mild activity against S. aureus, while compound 15 had mild activity towards S. aureus and C. albicans. However, no significant anticancer activity was observed with any of the tested compounds. From these results, we conclude that the presence of the spacer between the heterocyclic substituent and the benzofuran nucleus may be essential for the biological activity.

KDM3A promotes oral squamous cell carcinoma cell proliferation and invasion via H3K9me2 demethylation-activated DCLK1

Yang Lei,Zhang Qiqiong,Yang Qiuye 한국유전학회 2022 Genes & Genomics Vol.44 No.11

Background: Oral squamous cell carcinoma (OSCC) is a frequently-diagnosed malignancy with high potential for proliferation and invasion. Histone methylation is known as a crucial mechanism that regulates pathological processes in various cancers, including OSCC. Objective: This study sought to delve into the molecular mechanism of lysine demethylase 3 A (KDM3A) in OSCC cell proliferation and invasion. Methods: Expression levels of KDM3A, lysin-9 of di-methylated histone H3 (H3K9me2), and doublecortin-like kinase 1 (DCLK1) in cells were determined by reverse-transcription quantitative polymerase chain reaction or Western blot analysis. Cell proliferation and invasion were evaluated by cell counting kit-8, colony formation, and Transwell assays. The enrichment of KDM3A and H3K9me2 on the DCLK1 promoter was determined by chromatin immunoprecipitation assay. The functional rescue experiment was performed with DCLK1 overexpression vector and si-KDM3A in CAL-27 and SCC-9 cells. Results: KDM3A was elevated in OSCC cells. KDM3A knockdown suppressed OSCC proliferation and invasion, along with increased H3K9me2 level in OSCC cells. KDM3A and H3K9me2 were enriched on the DCLK1 promoter and inhibiting H3K9me2 improved DCLK1 expression levels. DCLK1 overexpression neutralized the inhibition of KDM3A knockdown on OSCC proliferation and invasion. Conclusions: KDM3A facilitated OSCC proliferation and invasion by eliminating H3K9me2 to upregulate DCLK1 expression levels.

2012년 부산 지역 인플루엔자바이러스의 월별 양상과 연령별 분포

전은미,허만규 한국자료분석학회 2015 Journal of the Korean Data Analysis Society Vol.17 No.2

Human influenza viruses in infants or young babies are important causes of upper respiratory tract illness and lower respiratory tract illness. A better understanding of influenza seasonality is useful to inform the timing and composition of vaccine recommendations and monitor the emergence of new virus variants. We tested influenza virus specimen in 2,421 hospitalized children of four hospitals in Busan to identify 3 kinds of respiratory viruses, influenza virus A (H1N1 and H3N2) and influenza virus B. Identification of viruses was used the indirect fluorescent test (IFA) with FITC-conjugated anti-mouse immunoglobulin and hemagglutination inhibition test (HI test). We analyzed the positive rate, annual frequencies according to the retrospective review of medical records. Of 1310 influenza virus A samples, 88 (7.0%) had positive. Of 88 positive influenza A virus samples, number of influenza H1N1 subtype was 31 (2.4%) and number of influenza H3N2 subtype was 57 (4.4%). The positive influenza virus B was 4.7% (52/1111). Positive respiratory viruses on January and February were detected 11.4% and 10.6%, respectively. The detection rates between males and females were similar pointing out each 1.3% out of specimens in 2012. As for the age distribution, the high detection rates were indicated in children at the age of two to five. 소아 및 유아에서 발병한 호흡기 인플루엔자바이러스 감염은 두통과 폐렴 등 여러 질병을 유발함으로 매우 중요하다. 인플루엔자의 계절별 동향과 세부 타입의 분류는 처방전에서 차이 등을 수반하므로 이들의 이해와 정보는 매우 유익하다. 부산 시내 2012년 4개 병원에서 수집한 2,421명의 소아 및 유아에서 발병한 호흡기 인플루엔자바이러스의 세부아형인 A형(H1N1, H3N2), B형을 동정하였다. 바이러스 동정은 FITC-접합한 항-마우스 면역글로블린을 이용한 간접면역형광법(IFA)과 헤마글루티네이션 억제법(HI test)으로 확인하였다. 의료기록에 근거한 연령별, 양성반응률, 연중 빈도를 분석하였다. 인플루엔자 바이러스 A형은 88건(7.0%)이 양성이었다. 88명의 환자에 대한 양성 인플루엔자 바이러스 A형 중 57건(4.4%)은 인플루엔자 H3N2세부아형이었다. 양성 인플루엔자B바이러스는 52건(4.7%)이었다. 양성 호흡기 바이러스에서 1월과 2월은 각각 11.4%, 10.6%였다. 한편, 부산지역의 4개 병원을 층(strata)으로 하여 각 병원 효과를 통제한 후 인플루엔자 유형과 감염비율이 연관성이 있는지 Cochran-Mantel-Haenzel 검정을 실시하였다. 먼저 Breslow-Day의 승산비 동질성 검정을 한 결과 각 병원의 오즈비가 동일하게 나왔으며(p=0.771) 병원 효과를 통제한 후 인플루엔자 유형과 양성반응 비율의 차이 검정을 종합적으로 분석한 결과 통계적으로 차이가 나타났다. 2011-2012년도 질병관리본부에서 3,785건의 분석결과와 비교시 인플루엔자 바이러스 A형과 B형의 빈도는 유사하였으나 A형 중 H1N1타입과 H3N2타입의 빈도는 유의한 차이가 있었다.

스타티스 '오션 블루'의 자가영양배양시 광도, 환기횟수 및 CO2 농도가 소식물체의 기내 생육에 미치는 영향

정기원,정병룡 (사) 한국생물환경조절학회 2002 생물환경조절학회지 Vol.11 No.3

Growth and development of Limonium spp. cean Blueplantlets were studied under, three levelsof photosynthetic photon flux (PPF), 70, 150 and 220mmol m-2 s-1, two levels of CO2 concentration,500 and 1000 mmol mol-1, and two levels of number of air exchanges per hour (NAEH), 0.1 h-1 and2.8 h-1. Explants were obtained from photomixotrophically-micropropagated plantlets. Four explantsper vessel were cultured under cool-white fluorescent lamps for 16 h d-1 at 25 1oC and 70~80% rel-ative humidity. In treatments of 2.8 h-1 NAEH, a 10 mm round hole made on the vessel cap was sealedwith a microporous filter and two CO2 concentrations in the culture rooms were provided from a liq-uefied CO2 tank. Fresh and dry weights, height, length of the longest root, number of leaves, and leafarea significantly increased with increasing PPF and especially, CO2 concentration. Growth wasenhanced by a 2.8 h-1 NAEH. Overall, treatment with a 220mmol m-2 s-1 PPF and a 1000mmol mol-1CO2 resulted in the most vigorous growth of Limonium spp. cean Blueplantlets.

2-Aminobenzamide로부터 Quinazoline 4-one계 유도체의 합성(Ⅲ) : Acid anhydride와의 반응 Reaction with Acid Anhydrides

서명은 梨花女子大學校 藥學硏究所 1991 藥學硏究論文集 Vol.- No.1

The reaction of 2-aminobenzamide with phthalic acid anhydride In dioxane produced a bicyclic product 2,8-dioxoisoindole(1.2.a) quinazoline (1) in addition to hydrolysis product 2(2-Carboxyphenyl)-1.2-2H-quinazoline-4-one(Ⅱ). The yields were 64% and 30% respectively. On the other hand, the same reaction in DMF afforded compound(Ⅰ) and 2(2N-dimethyl carbamyl phenyl)-1.4-2H-quinazoline-4-one(Ⅲ) in 30% and 60% yield respectively. The compound Ⅲ was also obtained by the reaction of compoundⅡ with dimethylamine. However the reaction of 2-aminobenzamide with neat succinic acid anhydride gave only bicycle product 2.8-oxopyrrolidine (2.1.a)-1.4-2H-quinazoline (Ⅳ) in 93%.

2-Aminoindan 및 cis- ( ${\pm}$ ) -4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one의 효율적 합성

김민우,마은숙,Kim, Min-Woo,Ma, Eun-Sook 대한약학회 2006 약학회지 Vol.50 No.6

1-Amino-5,6-dimethoxyindan hydrochloride was synthesized from 3- (3,4-dirnethoxyphenyl)propionic acid by intramolecular Friedel-Crafts acylation, oximation with hydroxylamine, and reduction with an overall yield of 74%. 2-Amino-5,6-dimethoxyindan hydrochloride was synthesized from 3-(3,4-dirnethoxyphenyl)propionic acid by intramolecular Friedel-Crafts acylation, oximation with isoamylnitrite, reduction in NaOH and reaction with HCI to form 5,6-dimethoxy-2-indanone, which was reacted with hydroxylamine and reduced with an overall yield of 42%. 5,6-Dimethoxyindan-1,2-dione-2-oxime, which was catalytically hydrogenated to afford cis-, and trans-1-amino-5,6-dimethoxyindan-1-ol as 3 : 1 ratio. This mixture was treated with Li and reacted with chloroacetyl chloride. Cis isomer was acylated and cyclized to synthesize rir -( ${\pm}$ )-7,8-dimethoxy-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one, but trans isomer was just acylated to form amide.