• Title/Summary/Keyword: NCI ring

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ON NCI RINGS

  • Hwang, Seo-Un;Jeon, Young-Cheol;Park, Kwang-Sug
    • Bulletin of the Korean Mathematical Society
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    • v.44 no.2
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    • pp.215-223
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    • 2007
  • We in this note introduce the concept of NCI rings which is a generalization of NI rings. We study the basic structure of NCI rings, concentrating rings of bounded index of nilpotency and von Neumann regular rings. We also construct suitable examples to the situations raised naturally in the process.

Design, Synthesis, and Preliminary Cytotoxicity Evaluation of New Diarylureas and Diarylamides Possessing 1,3,4-Triarylpyrazole Scaffold

  • Choi, Won-Kyoung;El-Gamal, Mohammed I.;Choi, Hong-Seok;Hong, Jun-Hee;Baek, Dae-Jin;Choi, Ki-Hang;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.33 no.9
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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.

Synthesis and Preliminary Cytotoxicity Evaluation of New Diarylamides and Diarylureas Possessing 2,3-Dihydropyrrolo[3,2-b]quinoline Scaffold

  • Kim, Hyun-Jin;El-Gamal, Mohammed I.;Lee, Yong Sup;Oh, Chang-Hyun
    • Bulletin of the Korean Chemical Society
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    • v.34 no.8
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    • pp.2480-2486
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    • 2013
  • A new series of diarylamides and diarylureas having 2,3-dihydropyrrolo[3,2-b]quinoline scaffold was synthesized. Their in vitro antiproliferative activities were tested over NCI-60 cancer cell lines of nine different cancer types. Some target compounds showed good inhibition percentages over different cell lines. Among all the target compounds, compound 1f possessing 6,7-dimethoxy-2,3-dihydropyrrolo[3,2-b]quinoline nucleus, amide linker, and 4-chloro-3-(trifluoromethyl)phenyl terminal ring showed high selectivity against MCF7 and MDA-MB-468 breast cancer cell lines more than the other tested cell lines. Its inhibition percentages at $10{\mu}M$ concentration over those two cell lines were 84.97% and 87.13%, respectively.

Pharmacophore Design for Anti-inflammatory Agent Targeting Interleukin-2 Inducible Tyrosine Kinase (Itk)

  • Chandrasekaran, Meganathan;Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Namadevan, Sundaraganesan;Kim, Hyong-Ha;Kim, Yong-Seong;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.31 no.11
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    • pp.3333-3340
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    • 2010
  • A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-inflammatory activities targeting Interleukin-2 inducible tyrosine kinase (Itk). 16 structurally diverse molecules were selected as training set to generate the hypotheses using Discovery Studio v2.1. The best hypothesis, Hypo1, comprises two hydrogen bond acceptor (HBA), one hydrophobic aromatic (HA), one ring aromatic (RA) and shows high cost difference (63.71), high correlation coefficient (0.97) as well as low RMS deviation (0.81). Hypo1 has been further validated toward a test set, decoy set and Fischer's randomization method. Furthermore, Hypo1 was used to screen NCI and Maybridge databases. Finally, 2 hit molecules were identified as potential leads against Itk, which may be useful for future drug development.

Studies on Anti-cancerous Substances from Higher Plane in East Asian Region

  • Takeya, Koichi
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 1999.10a
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    • pp.1-45
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    • 1999
  • To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for ncancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically Oridonin isolated from Rabdosia ssp.is now investigated for clinical trials in China. Moreover, camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity. This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifolia, has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential. Some efforts are continued in National Cancer Institute NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin III, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected in Japan, China, Korea, Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia in mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma (KB) cells in our laboratory, as primary screening. In this meeting, I will present on antitumor and cytotoxic substances of the higher plants (Rubia cordifolia, Ailanfhus Vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var drupacea, etc.) selected from above screening tests.

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Studies on Anti-Cancerous Substances from Higher Plants in East Asian Region

  • Takeya, Koichi
    • Plant Resources
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    • v.3 no.1
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    • pp.1-45
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    • 2000
  • To date many kinds of compounds have been obtained from plants kingdom as antineoplastic and anti-cancerous agents. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids. lignans, terpenes and steroids etc. Curcumol obtained from Curcuma aromatica was tested and noticed to be effective against cancer of the uterine cervix clinically. Oridonin isolated from Rabdosia ssp. is now investigate for clinical trials in China. Moreover camptothecine isolated from Camptotheca acuminata is also antineoplastic alkaloid, but is very toxic. Chemical modification has been tried to decrease its toxicity This compound is now using as clinical agent. Harringtonin was investigated as an anticancerous drug in China. Taxol, a compound with a taxane ring isolated from the bark of Taxus brevifotia. has been demonstrated to have substantial anticancer activity in patients with solid tumors refractory standard chemotherapy. Supply of this drug has severely limited full exploration of its antineoplastic potential Some efforts are continued in National Cancer Institute(NCI) Washington for surveying various Taxus species for optimal taxol content, improvement in semi-synthesis from baccatin 111, improvement in method of extraction, and development of alternative renewable resources. Further, there are many compounds which have been reported as antineoplastic agents. On the other hand, we have screened on higher plants collected In Japan, China, Korea. Southeast Asia and South America for antineoplastic activity, which has been done using Sarcoma 180 ascites in mice, P388 Iymphocytic leukemia In mice, Chinese hamster lung V-79 cells, P388 cells and nasopharynx carcinoma(KB) cells in our laboratory, as primary screening. In this meeting, 1 will present on antitumor and cytotoxic substances of the higher plants(Rubis cordifolia, Ailanthus vilmoriniana, Aster tataricus, Taxus cuspidata var. nana, Cephalotaxus harringtonia var. drupacea, etc.) selected from above screening tests.

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Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen

  • Moon, Seung Kee;Park, So Ra;Park, Ami;Oh, Hyun Mi;Shin, Hyun Jung;Jeon, Eun Ju;Kim, Seiwhan;Park, Hyun June;Yeon, Young Joo;Yoo, Young Je
    • Molecules and Cells
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    • v.39 no.3
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    • pp.217-228
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    • 2016
  • To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their antiproliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity ($IC_{50}$: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity ($K_D$: 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCIN82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.

Effect of Whalakyuoleyng-dan plus Yinsamyangwui-tang on Anti-angionesis (활락효영단합인삼양위탕(活絡效靈丹合人蔘養胃湯)이 혈관신생(血管新生) 억제(抑制)에 미치는 영향(影響))

  • Ko, Ki-Wan;Park, Joon-Hyuk;Kang, Hee;Kim, Sung-Hoon;Yu, Young-Beob;Shim, Bum-Sang;Choi, Seung-Hoon;Ahn, Koo-Seok
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.7 no.1
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    • pp.77-97
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    • 2001
  • Anti-angiogenesis is one of therapies which have been high-lightened on the research of cancer treatment. Anti-angiogenesis means that new blood vessels are created from a existing capillary tube and it is a important process on metastasis and permeation when cancer is created or formed. Since angiogenesis have been under research, a complete recovery oriented treatment against cancer have been suggested blocking metastasis, delaying the growth of cancer cell, and blocking the supply of oxygen and nutritive substance through the web of blood vessels. Until now, there are several anti-angiogenesis, which have been known to the public, such as thalidomide, angiostatin, endostatin, 2-methoxyestradiol, TNP-470, and marimastat, etc. Additionally, 17 clinical testing projects about anti-angiogenesis are on the process in NCI(National Cancer Institute). Especially, TNP-470 showed effectiveness against cancer on clinical testing after finishing animal testing. Based on existing researches showing that Yinsamyangwui-tang is effective to strengthening body resistance and Whallakhyolenyng-dan effects cells on the inside of blood vessel because Whallakhyolenyng- dan restrains cell adhesion during the restraining period of a blood vessel, I tried to research the effect of Whalakhyolenyng-dan plus Yinsamyangwui-tang on angiogenesis. I made a conclusion putting into operation through using SK-Hep-1 (KCLB 30052), A549(KCLB 10185), AGS(KCLB 21739), and BCE(Bovine Capillary Endothelial Cell). Followings are the results of my experimental research: 1. According to the researching results of anti-cancer activation against cancer cell, Whallkhyoleyng dan plus Yinsamyangwui-tang decreased the number of cancer cells -- While injecting $600{\mu}g/ml$, injected groups decreased 3.1% more comparing with the contrastive group of SK-Hep-1, 49.7% more comparing with the contrastive group of A549, and 31.0% more comparing with the contrastive group of AGS. 2. According to the researching results of DNA composition effect between BCE and cancer cell, Whallakhyoleyng-dan plus Yinsamyangwui-tang reduced the rate of SK-Hep-1 synthesis inhibition by 59.1% at $600{\mu}g/ml$ intensity comparing with contrastive group; for A549, 72.6%; for AGS, 6.1%, for BCE, 28.9%. 3. According to the researching results about the effect of BCE cell to angiogenesis, angiogenesis was restrained at $400{\mu}g/ml$ intensity during 18 hours observation. 4. In the case of aortic ring assay, the half level of angiogenesis was reduced comparing with the contrastive group while injecting with $400{\mu}g/ml$ intensity; with $800{\mu}g/ml$, under 10% comparing with contrastive group; and with $1600{\mu}g/ml$, complete restrain. According to the above results, Whallakhyoleyng-dan plus Yinsamyangwui-tang was proved to have an anti-angiogenetic effects.

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