• Title/Summary/Keyword: structure-activity relationship

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Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of Aglaia elliptica against P-388 Murine Leukemia Cells

  • Hidayat, Ace Tatang;Farabi, Kindi;Harneti, Desi;Maharani, Rani;Darwati, Darwati;Nurlelasari, Nurlelasari;Mayanti, Tri;Setiawan, Arlette Suzy;Supratman, Unang;Shiono, Yoshihito
    • Natural Product Sciences
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    • v.23 no.4
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    • pp.291-298
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    • 2017
  • Six dammarane-type triterpenoids, dammar-24-en-$3{\beta}$-ol (1), $3{\beta}$-epicabraleahydroxy lactone (2), (E)-25-hydroperoxydammar-23-en-$3{\beta}$,20-diol (3), dammar-24-en-$3{\beta}$,20-diol (4), $3{\beta}$-acetyl-20S,24S-epoxy-25-hydroxydammarane (5), and $3{\beta}$-epiocotillol (6) were isolated from the methanolic extract of the bark of Aglaia elliptica. The chemical structure were identified on the basis of spectroscopic evidence and by comparison with those spectra previously reported. Compounds 1 - 6 were isolated first time from this plant. Compounds 1 - 6, along with a known synthetic analog, cabraleone (7) were evaluated their cytotoxic activity against P-388 murine leukimia cells in vitro. Among those compounds $3{\beta}$-acetyl-20S,24S-epoxy-25-hydroxydammarane (5) showed strongest cytotoxic activity with $IC_{50}$ value of $8.02{\pm}0.06{\mu}M$.

Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors

  • Paudel, Suresh;Wang, Shuji;Kim, Eunae;Kundu, Dooti;Min, Xiao;Shin, Chan Young;Kim, Kyeong-Man
    • 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.

The Relationship between Structural Denaturation of Antioxidative Enzymes and Their Enzyme Activity due to Repeated Exposure to UV-A (UV-A 반복노출로 인한 항산화효소의 구조변성과 효소활성의 상관관계)

  • Park, Mijung;Yoo, Hyo Jung;Kim, Jong Chan;Kim, So Ra
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.1
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    • pp.75-81
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    • 2015
  • Purpose: The present study was conducted to investigate whether the changes in structure and activity of antioxidative enzymes, superoxide dismutase(SOD) and catalase(CAT) present in the eyes appeared when they were repeatedly exposed to UV-A, and reveal the correlation of these changes. Methods: Each enzyme solution was prepared from the standardized SOD and CAT, and repeatedly exposed to UV-A of 365 min under the condition of 30 minutes, 1 hour and 2 hours a day over 1, 2, 3, 4 and 5 days. Structural denaturation of SOD and CAT induced by repeat UV-A irradiation was confirmed by the electrophoretic analysis, and their enzyme activity was determined by the colorimetric assay using the proper assay kit. Results: SOD exposed repeatedly to UV-A showed the polymerization pattern through the electrophoretic analysis when it was repeatedly exposed under the condition of at least 1 hour a day however, the change of its activity was found to be less than 12%. On the other hand, CAT repeatedly exposed to UV-A showed reduced size of the electrophoretic band which indicated a structure denaturation and its activity was significantly decreased. In the case of that the repeat exposure time was longer, CAT activity was completely lost even though some enzyme band was shown in the electrphoretic analysis. Conclusions: From these results, it was revealed that the degree and pattern in structural denaturation of antioxidative enzymes differently appeared according to the type of enzyme, and the degree of structural denaturation was not always consistent with the reduction in enzyme activity.

A Study on the Expressional Characteristics and Kengo Kuma's Structure of Architectural Thinking as the Dynamic Criticism (쿠마켄고의 역동적 비평성으로서의 건축적 사고구조와 표현 특성에 관한 연구)

  • Kim, Yun-Jung;Park, Chan-Il
    • Korean Institute of Interior Design Journal
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    • v.22 no.5
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    • pp.114-125
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    • 2013
  • Kengo Kuma used to be very known well as a critic before being an architect. He usually mentioned quite unique type of comments for subjects whenever his criticism, also even his works results have been able to be targets of criticism materials by his method. His works are the achievements of challenges based on his continuous dynamic criticism. Hence, to have well understanding of his architectural thinking and works result, his complexes criticism structure must be needed to understand. And also, this study is using 'KJ Method' type to analyze his architectural thinking which is complicated making by a type of non-linear. Kengo Kuma's structures of architectural thinking and critiques perspective of modern architecture have been created by 'KJ Method'. Critiques types of keywords and consequences words collected from among the local dedicated professional architecture books to get this research result. First of all, Kengo Kuma desired even modern architecture problems to be melt as a specific architecture result such as modern type of power structure. To have result, Kengo Kuma had experienced sensible activity through materials which have specific characteristic. Also place of materiality created to get relationship between environments and architecture. Secondly, he wanted to recover troubled traditional Japanese architectural perspective which blocked relationship by dichotomy as a right way. In conclusion, this research reaches Kengo Kuma's type of architecture which strongly emphasizes harmony among related components such as human being, materials, substances based on accepted natural environments and lives' principle. Also, much more specific methods have been derived by related works results analyzing which have similar characteristic as Kengo Kuma's one.

Developing a Scale for Measuring the Constraints in Physical Activity of People with Physical Disabilities - Verification of Factor Structure and Related Criterion Validity - (지체장애인의 운동참여제약 측정척도 개발 -요인구조 탐색과 준거관련타당도 검증-)

  • Seo, Eunchul;Baek, Jae keun
    • 재활복지
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    • v.21 no.1
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    • pp.253-277
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    • 2017
  • The purpose of this study was to develop the Constraints in Physical Activity Scale for people with physical Disabilities(CPASD) which measures the constraints in physical activity of people with physical disabilities. For this study, the 5 step analytic framework of unified validity developed by Messick (1995), the framework for conducting a strong program of construct validation by Benson (1998) method were applied. Furthermore, the validity of CPASD was systematically presented by applying common factor model and measurement model to 264 persons with physical disabilities. The conclusion based on the results and discussions of this study is as follows. First, CPASD presented evidence of job validity. Four factors (17 items) were developed, consisting of leader constraints, economic constraints, prejudice, and exercise environment constraints through the analysis of the factor structure and the fit of factor coefficients. Second, the factor structure of the developed CPASD (leader constraint, economic constraint, prejudice, exercise environment constraint) was statistically distinguished and stably reflected the existing exercise participation constraints theory. Third, the developed CPASD presented evidence of the validity of the criteria. Leader constraints and prejudice were negatively correlated with positive motor emotions, leader constraints, prejudice, and exercise environment constraints were positively correlated with negative motor emotions. Therefore, in future research, it is necessary to reevaluate the current system and actual condition related to leader constraints, economic constraints, prejudices, and exercise environment constraints derived as factors of CPASD. To do this, it is necessary to judge the degree of reality based on the causal relationship verification and IRT theory using CPASD.

Herbicidal Activity and Persistency in Aqueous Solution of Ortho Disubstituted Benzenesulfonyl Urea Derivatives (새로운 Ortho 이치환 Benzenesulfonyl Urea 유도체의 제초활성과 수용액중의 잔류성)

  • Kim, Yong-Jip;Chang, Hae-Sung;Kim, Dae-Whang;Sung, Nack-Do
    • Applied Biological Chemistry
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    • v.38 no.6
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    • pp.570-576
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    • 1995
  • The new sixteen herbicidal N-2-(1-hydroxy-2-fluoroethyl)-6-substituted(X)-benzenesulfonyl-N'-4,6-dimethoxypyrimidinyl-2-yl urea derivatives(S) were synthesized and thier herbicidal activities$(pI_{50})$ in vivo against rice(Orysa Sativa L.), Barnyard grass(Echninochloa orizicola) and Bulrush(Scirpus juncoides) were measured by the pot test under paddy conditions. The structure activity relationship(SAR) were studied using the physicochemical parameters of ortho-substituents(X) and hydrolysis rate constant(logk) and herbicidal activities by the multiple regression technique. The SAR suggested that the herbicidal activities were more dependant on the hydrolysis rate constant(logk>0) than the steric constants $(Es, small width($B_4$) and length($L_1$). Among them, halogens(2 & 5), methyl(15) and non(H) substituent(1) showed higher herbicidal activity for weeds which was not tolerent to rise and weeds. The herbicidal activity was increased and the persistency in aqueous solution was decreased by electron donating(${\sigma}0<0$) groups as ortho-substituent(X). From the relationship equation between herbicidal activity and hydrolysis rate constant, it was assumed that the both reactions would be proceeds with similar process. And the conditions on the ortho substituents to show higher herbicidal activity and the persistency in aqueous solution were also discussed.

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Effect of Mosaic Vegetation Structure on Pine Seed Predation by Forest Animals in Agricultural Landscape (농촌경관내의 삼림동물에 의한 소나무종자 포식에 미치는 모자이크형 식생구조의 영향)

  • 홍선기;임영득
    • The Korean Journal of Ecology
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    • v.20 no.4
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    • pp.265-274
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    • 1997
  • All landscapes are mosaics of habitat patches of different types. Therefore, there are always edged between habitat patches in a landscape. Forest animal has an important role in vegetation development and maintenance by seed dispersal around forest. Movement of animals depends on the spatially heterogeneous structure and pattern of vegetation landscapes because each animal has special habitats in a landscape. Especially, forast edge with high permeability and prey density is one of the important habitats to the animals. Therefore, understanding the ecological characteristics of the forest edges as a corridor connecting mosaic vegetation patches is necessa교 새 establish the strategies for the nature conservation and sustainable vegetation management. Under this idea, we examined the animal influenced on pine seeds as one of the method of monitoring the animal activity in mosaic vegetation. Man-made mosaic vegetations including open, edge and inner forests were carefully selected in the rural landscape. We carried out predation test on pine seeds during one year. A result was that damages on seed was more significant at forest edge than inner and open forest. Pine seed on seedbeds was mainly attacked by squirrels and mice than birds. Pine seed was damaged by squirrels in different types of vegetation by seasons. Rate of seed predation at forest edge was, in special, higher than that of other sites. According to this results, it is suggested that the relationship between animal behavior and spatial vegetation structure relating to human impact such as the distance from settlement to vegetation appeares to be in the rural vegetation landscape.

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CONSTRUCTABILITY IMPLEMENTATION MODEL USING DEPENDENCY STRUCTURE MATRIX

  • Youngjib Ham;Moonseo Park;Hyun-Soo Lee
    • International conference on construction engineering and project management
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    • 2011.02a
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    • pp.550-555
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    • 2011
  • Utilizing construction knowledge and experiences in design phase can reduce change orders and improve productivity in construction phase. To do so, information must be made available to the design team in time. Current approaches for effective utilization of constructability knowledge, however, only focus on the formalization of constructability knowledge such as a checklist, which lacks the consideration of the appropriate use at the proper point in time. The inadequate use of constructability knowledge can result in unnecessary reworks. To deal with this problem, the design team needs to know what constructability knowledge is required for specific design activities in the design process. This paper presents a constructability implementation model using the dependency structure matrix (DSM) that focuses on information flows between design activities and constructability knowledge. For this objective, design activities in the design process are modeled in a matrix form based on their dependency. Then, constructability knowledge, which needs to be considered in the design stage, is mapped into activities and incorporated into the matrix, creating Constructability-DSM (C-DSM). Next, the partitioning algorithm is applied to C-DSM for optimal information flow. The Partitioned C-DSM is then analyzed based on the relationship between activities. Finally, the optimal utilization of construction knowledge in the design process is determined by identifying what constructability knowledge is required for each design activity, and how and when it is reflected to design for constructability. Thus, this research can help provide robust control actions to reduce unnecessary iterative cycles in design process for efficient constructability implementation.

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Preparation and Antioxidant Activities In Vitro of a Designed Antioxidant Peptide from Pinctada fucata by Recombinant Escherichia coli

  • Wu, Yanyan;Ma, Yongkai;Li, Laihao;Yang, Xianqing
    • Journal of Microbiology and Biotechnology
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    • v.28 no.1
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    • pp.1-11
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    • 2018
  • An antioxidant peptide derived from Pinctada fucata meat using an Alcalase2.4L enzymatic hydrolysis method (named AOP) and identified by LC-TOF-MS has promising clinical potential for generating cosmetic products that protect skin from sunshine. To date, there have been few published studies investigating the structure-activity relationship in these peptides. To prepare antioxidant peptides better and improve their stability, the design and expression of an antioxidant peptide from Pinctada fucata (named DSAOP) was studied. The peptide contains a common precursor of an expression vector containing an ${\alpha}$-helix tandemly linked according to the BamHI restriction sites. The DNA fragments encoding DSAOP were synthesized and subcloned into the expression vector pET-30a (+), and the peptide was expressed mostly as soluble protein in recombinant Escherichia coli. Meanwhile, the DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity of DSAOP $IC_{50}$ values were $0.136{\pm}0.006$, $0.625{\pm}0.025$, and $0.306{\pm}0.015mg/ml$, respectively, with 2-fold higher DPPH radical scavenging activity compared with chemosynthesized AOP (p < 0.05), as well as higher superoxide radical scavenging activity compared with natural AOP (p < 0.05). This preparation method was at the international advanced level. Furthermore, pilot-scale production results showed that DSAOP was expressed successfully in fermenter cultures, which indicated that the design strategy and expression methods would be useful for obtaining substantial amounts of stable peptides at low costs. These results showed that DSAOP produced with recombinant Escherichia coli could be useful in cosmetic skin care products, health foods, and pharmaceuticals.

Antibacterial Activity of Pinus densiflora Leaf-Derived Components Toward Human Intestinal Bacteria

  • Hwang, Young-Hee;Lee, Hoi-Seon
    • Journal of Microbiology and Biotechnology
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    • v.12 no.4
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    • pp.610-616
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    • 2002
  • The growth-inhibiting effects of Pinus densiflpora leaf-derived materials on nine human intestinal bacteria were investigated using the impregnated paper disk method, and their activities were compared with those of 13 commercially available terpenes. The biologically active constituent of the extract of P densiflora leaf was characterized as the monoterpene (1R)-(+)-$\alpha$-pinene by various spectroscopic analyses. Responses varied according to bacterial strain, chemicals, and dose. At 10 mg/disk, limonene and (1R)-(+)-$\alpha$-pinene strongly inhibited the growth of Clostridium perfringens, Staphylococcus aureus, and Escherichia coli, without adverse effects on the growth of five lactic acid-bacteria (Bifidobacterium adolescentis, B. bifidum, B. longum, Lactobacillus acidophilus, and L. casei). Little or no inhibition against seven bacteria was observed with anethole, borneol, camphor, caryophyllene, 1,8-cineole, estragole, linalool, and $\alpha$-terpineol. Structure-activity relationship revealed that (1R)-(+)-$\alpha$-pinene had more growth-inhibiting activity against C. perfringens than (1R)-(+)-$\beta$-, (1S-(-)-$\alpha$-, and (1S-(-)-$\beta$-pinenes. Furthermore, the growth-inhibition against L. casei was much more pronounced in (1R)-(+)-$\beta$- and (In-(-)-$\beta$-pinenes than (1R)-(+)-$\alpha$- and (1S)-(-)-$\alpha$-pinenes. These results indicate that the (+)-$\alpha$ form seems to be required against C. perfringens and $\beta$ form against L. casei for growth-inhibiting activity. Morphologically, most strains of C. perfringens were damaged and disappeared at 5 and 2 mg/disk of (1R)-(+)-$\alpha$-pinene. Morphological study revealed that (1R)-(+)-$\alpha$-pinene had more growth-inhibiting activity against C. perfringens than (1R)-(+)-$\beta$-, (1S)-(-)-$\alpha$-, and (1S)-(-)-$\beta$-pinenes. As naturally occurring growth-inhibiting agents, the Pinus leaf-derived materials described above could be useful preventive agents against diseases caused by harmful intestinal bacteria such as clostridia.