• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1994.11a
• /
• pp.99-104
• /
• 1994

Renin-Angiotensin계는 정상 및 질병시의 혈압조절에 매우 중요한 역할을 담당하고 있음이 밝혀지면서, 이 조절계의 특정단계를 간섭함으로써 새로운 고혈압치료제를 개발하려는 연구가 일찍부터 시도되었다. (그림 1). 그 중에서 내인성 생리활성물질인 Angiotensin II의 합성을 차단하는 ACE 저해제는 임상적으로 고혈압 및 심부전치료제로서 유용성이 인정되어 현재 널리 사용되고 있다. ACE 저해제는 종종 마른기침, 발적과 같은 부작용이 나타나므로 이러한 부작용을 극복하려는 연구가 많이 있었으나 이는 작용기전에서 기인되는 것으로 해결에 한계를 보여왔다. 그런데 1982년 일본의 Takeda사의 연구진은 S-8307, 8308이라는 효과가 매우 약하기는 하지만 Angiotensin II 수용체를 선택적으로 차단하는 비펩타이드성의 AII길항물질을 특허 출원하였다. 미국의 Du Pont사는 AII길항약물이 효능은 그대로 유지하면서 ACE 저해제들의 부작용을 해결할 수 있을 것으로 예상하고 Takeda 화합물을 모핵으로하여, 많은 유도체들을 합성하면서 구조-활성 연구를 수행한 결과 비펩타이드성길항제인 Dup 753(Losartan, Cozaar$^{R}$) (2-N-butyl-4-chloro-5-hydroxymethyl-1-(2'-(1H-tetrazole-5-yl)biphenyl-4-yl) imidazole, potassium salt)을 발견하게 되었다. 이 Dup 753은 특별히 AII수용체중 혈압조절과 관련이 있는 AT1 수용체를 선택적으로 차단하는데, 효력은 ACE 저해제인 captopril과 유사하며, 경구흡수가 잘되고 지속시간이 길어 하루에 한번 먹는 경구제제로 개발되고 있는 것으로 알려져 있다. 이 Dup 753의 지속시간이 긴 것은 그 대사물인 Exp 3174에 기인하는 것으로 알려져 있으며, 대사체가 Dup 753에 비해 효력도 훨씬 더 높고 지속시간도 길어서, Dup 753은 일종의 prodrug적 개념이 들어있는 약물이라 할 수 있다.

• Journal of Life Science
• /
• v.13 no.6
• /
• pp.843-848
• /
• 2003

Diarrllea and death of chicken have been brought about by fowl typhoid caused by Salmonella gallinarum, which causes a great loss of chicken farms. For the development of the probiotic which can control a fowl typhoid of S. gallinarum without any adverse effect of commercial existing antibiotics, we isolated antagonistic intestinal bacteria against S. gallinarum from a bowel of the chicken which was pastured in a chicken farm of Gumi, Kyoungbuk. An Y3 strain which had a strong antagonistic ability to S. gallinarum was selected as a candidate of chicken probiotic microorganism among isolated strains. It was identified as a Bacillus amyloliuefaciens by 98% similarity by the result of cultural, physiological, biochemical test and Biolog system$(Microlog^{TM} 4.0)$, and named as Bacillus amyloliquefaciens Y3. The strain showed the strongest antagonistic activity and a good growth at pH 5-9, $37^{\circ}C.$

• Korean journal of applied entomology
• /
• v.61 no.1
• /
• pp.101-108
• /
• 2022

Because of their specificity to target insects and relatively low toxicity to non-target organisms, insect growth regulators (IGRs) have been regarded as attractive alternatives to chemical insecticides. Commercially available IGRs are classified into juvenile hormone agonists (JHAs), ecdysone agonists (EAs), and chitin synthesis inhibitors (CSIs) according to their mode of action. Recently, JH-mediated interaction of methoprene-tolerant (Met), which is JH receptor, and its binding partners have been replicated in vitro using yeast cells transformed with the Met and FISC/CYC genes of A. aegypti. Using this in vitro yeast two-hybrid β-galactosidase assay, juvenile hormone antagonists (JHANs) have been identified from various sources including chemical libraries, plants, and microorganisms. As juvenile hormone (JH) is an insect specific hormone and regulates development, reproduction, diapause and other physiological processes, JHANs fatally disrupt the endocrine signals, which result in abnormal development and larval death. These results suggested that JHANs could be efficiently applied as IGR insecticides with a broad insecticidal spectrum. This review discuses JH signaling pathway mediated by Met and future prospects of JHANs as environmentally benign IGR insecticides.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.41 no.3
• /
• pp.243-252
• /
• 2015

Melanosome, the pigment granule in melanocyte, determines the color of skin when it moves into the keratinocyte. Inhibition of melanosome transfer from melanocyte to keratinocyte results in skin depigmentation. Protease activated receptor-2 (PAR-2) is involved in signal transduction systems via cell membrane and increases the melasome transfer when it is activated by cleavage of their extracellular amino acid sequence by trypsin or by a peptide such as SLIGKV. Here, we showed that lobaric acid inhibited PAR-2 activation and affected the mobilization of $Ca2^+$. The uptake of fluorescent microspheres and isolated melanosomes from melan-a melanocytes to keratinocytes induced by SLIGKV were inhibited by lobaric acid. Also, confocal microscopy studies illustrated a decreased melanosome transfer to keratinocytes in melanocyte-keratinocyte co-culture system by lobaric acid. In addition, lobaric acid induced visible skin lightening effect in human skin tissue culture model, melanoderm$^{(R)}$. Our data suggest that lobaric acid could be an effective skin lightening agent that works via regulation of phagocytic activity of keratinocytes.

• Applied Biological Chemistry
• /
• v.47 no.1
• /
• pp.27-32
• /
• 2004

The antagonistic microorganisms against Salmonella gallinarum causing fowl typhoid were isolated from the gut of wild pheasant. The isolated L19, L33, L50 strains were showed the characteristics of isolated Gram negative, rods, catalase positive and oxidase negative. Finally, all strains were identified as Sphingomonas sanguis by $Biolog^{\circledR}$ system. The optimal carbon sources of Sphingomonas sanguis L19, L33 and L50 for the these growth ~ere glucose, saccharose, and fructose respectively. But the optimal carbon sources of S. sanguis L19,L33, L50 for the antagonistic material production were maltose, galactose, and saccharose respectively. The optimal nitrogen sources of S. sanguis L19, L33, L50 for the growth were yeast extract, yeast extract, and $NH_4H_2PO_4$ respectively. But the optimal nitrogen sources of S. sanguis L19, L33 and L50 for the antagonistic material production were $(NH_4)_2SO_4$ urea, $(NH_4)_2S_2O_8$ espectively.

• Korean journal of applied entomology
• /
• v.31 no.4
• /
• pp.475-479
• /
• 1992

The non-steroidal ecdysone agonist RH 5849 showed almost similar LC.o values( 18.1-26.5 ppm) at all stages of larval development of the tobacco cutworm, Spodoptera litura, when treated by a leaf-disk dipping method. The feeding-inhibition rate for the 4th instar larvae was dose-dependent, and simultaneously the weight gain of 3rd instar larvae ceased within 48 hour after feeding of the cabbage leafdisk dipped into RH 5849 4.2 ppm solution. The systemic larvicidal effect of RH 5849 was compared at cabbage and tobacco whole plant test. The $LC_{50}$ values below 20 ppm(mg/kg soil) was lasted for 15 days in cabbage, 30 days in tobacco respectively.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1995.04a
• /
• pp.60-60
• /
• 1995

새로운 혈소판 활성화인자 (PAF) 수용체 결합 저해활성 유효성분인 pinusolide ($IC_{50}$/=2.5$\times$$10^{-7}$M)와 arctigenin($IC_{50}$/=5.2$\times$$10^{-6}$M)을 측백엽(Biota orientalis)과 우방자(Arctium lappa)로부터 분리하여 이미 보고한 바 있다. PAF 수용체에 대한 구조활성 상관관계를 규명하고자 또한 용해도가 우수한 강력한 PAF 길항제를 개발하고자 이 길항제들의 유도체들을 다양한 유기화학반응을 이용하여 합성하였고 in vitro PAF receptor binding assay로 그 활성의 강도를 비교 검토하였다. 그 결과, lactone ring 부분은 unsaturated lactone이 saturated lactone보다 활성이 강하였고 ring이 개열되면 활성이 현저히 감소하였다. pinusolide 경우 exocylclic double bond 부분은 sp$^2$구조의 hydrophobic한 유도체가 활성이 강하였으며, methyl ester 부분은 hydrophobic한 유도체가 활성이 강하였다. Arctigenin의 경우 aromatic unit가 hydrophobic할수록 활성이 강하였다.

• Journal of the Korea Convergence Society
• /
• v.8 no.1
• /
• pp.115-121
• /
• 2017

AHR is a transcription factor activated by aryl hydrocarbons, regulating the expression of XMEs (xenobiotics Metabolizing Enzymes). Even though the role of AHR in human physiology has been intensively investigated for the past decades, our understandings are still largely limited due to the deficiency of adequate chemical agents. In addition, it has been demonstrated that AHR correlates to pathogeneses for some diseases. Furthermore, emerging data suggest that the study on the AHR may provide a valid therapeutic target. Classical antagonists in current use are reported to be partial agonistic whereas a pure antagonist is demanded. In this study, o-toluidinyl ring structure of 2-methyl-4-(2-methylphenyldiazenyl)phenyl picolinamide has been modified into various structures to optimize the AHR antagonistic activity by means of convergence study of organic synthesis and molecular biology.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1992.05a
• /
• pp.43-43
• /
• 1992

최근 수년 전부터 학습(learning), 기억(memory)의 분자약리학적 기전과 치매(dementia)의 신경생리학적 원인 규명에 대한 연구가 사회적 요구에 부응하여 증가하고 있다. 이에 본 연구에서는 횐쥐를 이용하여 실험실적 건망모델을 설정하여 항치매 물질의 효력 screening을 시도하였다. 실험실적 건망모델은 다음 두 가지 방법으로 설정하였다. 첫째, Acetylcholine 길항제인 Scopolamine을 사용하여 중추신경계중 기억, 학습기전과 관련된 것으로 알려진 cholinergic신경계률 차단하여 유발한 실험적 건망모델과, 둘째, 단백질합성 저해제인 cycloheximide를 사용하여 기억, 학습경로에 관여하는 수종의 중추 단백질듈을 비선택적으로 저해하여 유발한 실험적 건망모델을 이용하여 인삼, 오미자등의 항치매 효과를 검색하고자 수동적 회피학습능, 능동적 회피학습능, 자발운동량을 측정하여 기억, 학습, 행동의 상관 관계를 고찰하였다.

• Journal of Food Hygiene and Safety
• /
• v.38 no.5
• /
• pp.305-310
• /
• 2023

This study aimed to determine the human androgen receptor (AR)-mediated endocrine disrupting potential of parabens and triclosan in food and household products using a cell-based assay in the OECD TG No.458, the 22Rv1/MMTV_GR-KO transcriptional activation assay. Four parabens (methyl-, ethyl-, propyl-, and butyl-) are determined as AR antagonists in OECD TG No.458. However, their AR antagonistic effects were not exhibited in the presence of the S9 hepatic fraction. Triclosan is also classified as an AR antagonist, and the AR antagonistic effect induced by triclosan significantly decreased in the presence of the phase I + II S9 fraction. Regarding the mechanism of AR antagonism induced by parabens and triclosan, the AR-mediated endocrine disrupting effects were exhibited through suppressing the translocation of ligand-bound AR to the nucleus via blocking of AR dimerization in the cytosol. These results indicate that the four parabens and triclosan have AR-mediated endocrine disrupting potential through an AR antagonistic effect via inhibiting AR dimerization; however, their endocrine disrupting effects deceased in the presence of hepatic metabolic enzymes.