• Bulletin of the Korean Chemical Society
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• 제14권5호
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• pp.594-598
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• 1993

The protonation constants of the 14-membered tetraaza macrocycles A(3,14-dimethyl-2,6,13,17-tetraazatricyclo$[l6.4.0^{1,18}.0^{7,12}]$docosane) and B(2,3,6,13,14,17-hexamethyl-2,6,13,17-tetraazatric yclo-[l6.4.$0^{1,18}.0^{7,12}$]docosane) were measured by potentiometry. The formation constants of each of these ligands with copper(II) and nickel(II) were determined by an out-of-cell spectrophotometric method. The results indicate that the per-N-methylated macrocycle B exhibits much higher selectivity for complex formation with copper(II) over nickel(II) ion than A and other related 14-membered tetraaza macrocycles. The effects of the N-and C-substituents on the basicity and the metal ion selectivity of the ligands are discussed. The synthesis and properties of copper(II) and nickel(II) complexes of B are also described.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.94.2-94.2
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• 2003

CJ-11668 is a new potent and selective COX-2 inhibitor. CJ-11668 showed COX-2 inhibition (IC50) of 65nM and selectivity ratio (COX-l/COX-2) of 770 in the cell based assay. In the human whole blood assay, CJ-11668 showed COX-2 inhibition (IC50) of 370nM and selectivity ratio (COX-l/COX-2), 135. The treatment of CJ-11668 (5 mg/kg, p.o) produced a significant inhibition (35%) of inflamed rat paw volume in the carrageenan-induced acute inflammation. CJ-11668 also suppressed the PGE2 level (69% inhibition, 1 mg/kg, p.o) in the zymosan-induced mouse air pouch model after 3 hrs. (omitted)

• 한국안광학회지
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• 제18권4호
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• pp.533-540
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• 2013

목적: 본 연구에서는 발생 중[태어난 지 5일(P5), 10일(P10)] 마우스 망막의 ON-OFF 방향특이성 신경절세포 수상돌기 상에서 NMDA R1 수용체의 시냅스 패턴을 연구하고자 하였다. 방법: ON-OFF 방향특이성 신경절세포는 Lucifer yellow를 주사하여 형태학적 특징으로 동정하였다. 이극세포로부터의 글루타메이트의 흥분성 유입을 확인하기 위해 membrane traffic motor 단백질 마커인 kinesin을 이용하였다. 결과: 본 연구에서 P5, P10의 ON-OFF 방향특이성 신경절세포를 동정할 수 있었으며, NMDA R1의 면역반응반점은 내망상층에서 강하게 나타났다. ON-OFF 방향특이성 신경절세포의 수상돌기상의 수용체의 분포패턴에서 방향특이성을 예측할 수 있는 어떠한 비대칭성도 발견하지 못하였다. 결론: 이극세포로부터의 글루타메이트성 자극유입은 P5, P10 단계에서 모두 균형적으로 유입되며, 방향특이성은 NMDA R1 수용체의 특이적인 패턴에 있지 않음을 밝혔다.

• BMB Reports
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• 제46권2호
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• pp.97-102
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• 2013

The use of various cancer cell lines can recapitulate known tumor-associated mutations and genetically define cancer subsets. This approach also enables comparative surveys of associations between cancer mutations and drug responses. Here, we analyzed the effects of ~40,000 compounds on cancer cell lines that showed diverse mutation-dependent sensitivity profiles. Over 1,000 compounds exhibited unique sensitivity on cell lines with specific mutational genotypes, and these compounds were clustered into six different classes of mutation-oriented sensitivity. The present analysis provides new insights into the relationship between somatic mutations and selectivity response of chemicals, and these results should have applications related to predicting and optimizing thera-peutic windows for anti-cancer agents.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.524-528
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• 1999

cis-Annonacin (1) and the mixture of (2,4)-cis-and trans-isoannonacins (2 and 3), three known mono-tetrahydrofuran annonaceous acetogenins, have been isolated form the seeds of Annona cherimolia by the use of the brine shrimp lethality test (BST) for bioactivity directed fractionation. Their structures were elucidated based on spectroscopic and chemical methods. 1 showed potent cytotoxicities in the brine shrimp lethality test (BST) and among six human solid tumor cell lines with notable selectivity for the pancreatic cell line (PaCa-2) at about 1,000 times the potency of adriamycin. The mixture of 2 and 3 is over 10,000 times cytotoxic as adriamycin in the pancreatic cell line (PaCa-2). All of the compounds are about 10 to 100 times as cytotoxic as adriamycin in the prostate cell line (PC-3).

• The Korean Journal of Physiology and Pharmacology
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• 제13권1호
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• pp.61-70
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• 2009

We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on $Ba^{2+}$ blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary(CHO) cells and used the whole cell patch-clamp technique to record $K^+$ currents in the absence and presence of externally applied $Ba^{2+}$. Wild type Kir2.1 was blocked by externally applied $Ba^{2+}$ in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of $Ba^{2+}$ blockage. The estimated $K_d(0)$ was 108 ${\mu}M$ for Kir2.1 wild type, 124 ${\mu}M$ for a concatameric WT-Y145V dimer, 109 ${\mu}M$ for a WT-Y145L dimer, and 267 ${\mu}M$ for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for $Ba^{2+}$, also showing two components with very different time courses. Mutants D172K and D172R(lining the central, aqueous cavity of the channel) showed both a decreased affinity to $Ba^{2+}$ and a decrease in the on transition rate constant(${\kappa}_{on}$). These results imply that residues stabilising the cytoplasmic end of the selectivity filter(T141, S165) and in the central cavity(D172) are major determinants of high affinity $Ba^{2+}$ blockage in Kir 2.1.

• 동의생리병리학회지
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• 제21권1호
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• pp.82-85
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• 2007

The Chinese medicinal plant Artemisia annua is the source of the antimalarial compound artemisinin. By the way, Artemisin annula was known have endoperoxide ring structure is included and has anti-malarial effect. Malaria and Toxoplasma gondii (T. gondii) is belong to Apicomplexa genera. So, confirmed whether we go compound 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane that have endoperoxide ring structure and there is anti-toxoplasmosis effect. The efficacy of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2] nonane alone was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were peformed with HeLa cell cultures, with quantification of Toxoplasma growth by a cell proliferation assay. Selectivity of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane was 4.9 in vitro cell proliferation assay, this is higher than sulfadiazine (selectivity was 1.63). For in vivo studies, mice were acutely infected intraperitoneally with 10$^5$ tachyzoites of the virulent RH strain and then treated perorally for 4 days from 6 hours postinfection. Efficacy was assessed by sequential determination of parasite burdens in peritoneal cavity. in vitro, 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane inhibited Toxoplasma growth at a concentration of 150mg/kg of body weight per day, the inhibition ratio was estimated to be 85.72%.

• Journal of Microbiology and Biotechnology
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• 제28권2호
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• pp.323-329
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• 2018

In Escherichia coli, the transcription of genes related to metal homeostasis is activated by the presence of target metals. The promoter regions of those genes can be fused with reporter genes to generate whole-cell bioreporters (WCBs); these organisms sense the presence of target metals through reporter gene expression. However, the limited number of available promoters for sensing domains restricts the number of WCB targets. In this study, we have demonstrated an alternative method to generate novel WCBs, based on the notion that since the sensing mechanisms of WCBs are related to metal transportation systems, their properties can be modulated by disrupting metal homeostasis. Mutant E. coli strains were generated by deleting the znt-operon genes zntA, which encodes a zinc-export protein, and zntR, which encodes a znt-operon regulatory protein, to investigate the effects on the metal-sensing properties of WCBs. Deletion of zntA increased the sensitivity but abolished the selectivity of cadmium-sensing WCBs, whereas arsenic-sensing WCBs gained sensitivity toward cadmium. When zntR was deleted, cadmium-sensing WCBs lost the ability to detect cadmium, and this was recovered by introducing exogenous zntR. In addition, the metal-binding site of ZntR was genetically engineered to modulate metal selectivity. This study provides a valuable platform for the development of novel E. coli-based WCBs.

• Bulletin of the Korean Chemical Society
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• 제33권9호
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• pp.2991-2998
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• 2012

A series of new diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was synthesized and their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 9, 11, 12, 14, and 17-21 showed superior potency against A375P to Sorafenib. Over the NCI-60 cancer cell line panel, compound 14 possessing a methoxy group, amide linker, and 4-chloro-3-(trifluoromethyl)phenyl terminal ring showed the highest potency and broad-spectrum anticancer activity. Compound 13 showed high selectivity towards leukemia subpanel over other cancer types.

• 공업화학전망
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• 제24권6호
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• pp.32-40
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• 2021

세포 투과성 펩타이드(cell penetrating peptide; CPP)는 강력한 세포막 투과성을 보유하고 있어 난투과성 중거대분자 약물의 세포 내 전달체 개발에 있어 중요한 요소 기술로 부각되고 있다. 하지만 대부분의 세포 투과성 펩타이드는 타겟 세포에 대한 선택성 없이 투과하므로, 전신 투여시 심각한 부작용이 발생할 수 있다. 이 글에서는 선택적 세포 투과성 펩타이드를 개발하는 최근 연구 전략 중, 타겟 세포 표면에 존재하는 수용체에 결합하는 리간드를 이용한 전략과, 타겟 세포 주변의 물리, 화학, 생물학적 신호 변화를 이용하는 전략에 대해 소개한다. 특히, 최근 논문에 발표된, 어피버디(affibody)와 세포 투과성 펩타이드 결합체를 이용하여 HER2 수용체를 지닌 유방암 세포에 선택적 투과성을 부여하는 방법과, 암세포 주변의 작은 pH 변화를 감지하여 양전하성을 조절함으로써 수용체가 없는 유방암 세포에도 선택적으로 투과성을 보이는 방법에 대해 자세하게 소개한다.