-
[show abstract]
[hide abstract]
ABSTRACT: A series of new diarylurea and diarylamide derivatives possessing acet(benz)amidophenyl scaffold was synthesized. Their in vitro antiproliferative activity was tested against A375P human melanoma cell line. Compounds 1c,d and 2c,d showed the highest potencies with IC(50) values in sub-micromolar scale. In addition, compounds 1b,e,l and 2e,l were more potent than Sorafenib but with IC(50) values in micromolar range. Moreover, compound 2c was equipotent to Vemurafenib, and 2d showed higher potency than Vemurafenib against A375P. Molar refractometry calculation and ADME profiling of the highest potent four derivatives 1c,d and 2c,d are also reported.
Bioorganic & medicinal chemistry letters 03/2012; 22(9):3269-73. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3-(trifluoromethyl)phenyl) ureido)-2-methylbenzamide 7c exhibited potent activities (GI(50)=0.27 μM). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC(50)=0.26 μM, IC(50)=0.11 μM, respectively), showing a possibility as melanoma therapeutics.
Bioorganic & medicinal chemistry 02/2011; 19(6):1915-23. · 2.82 Impact Factor
-
Junsang Lee,
Bong Soo Nam, Hwan Kim,
Chang-Hyun Oh,
So Ha Lee,
Seung Joo Cho,
Tae Bo Sim,
Jung-Mi Hah,
Dong Jin Kim,
Jinsung Tae,
Kyung Ho Yoo
[show abstract]
[hide abstract]
ABSTRACT: The synthesis of a novel series of aminoquinazoline derivatives 1a-r and their antiproliferative activities against A375 human melanoma cell line were described. Among them, six compounds showed superior antiproliferative activities to Sorafenib as a reference compound. In particular, the representative compound 1q bearing chromen-4-one moiety exhibited excellent antiproliferative activity (IC(50)=0.006 μM) and good selectivity over HS27 fibroblast cell line.
Bioorganic & medicinal chemistry letters 10/2010; 20(19):5722-5. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The synthesis of a novel series of 1,4-dihydropyrazolo[4,3-d]imidazole phenyl derivatives 1a-b, 2a-v and their antiproliferative activities against A375P and WM3629 human melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, pyrazoloimidazole phenyl urea compounds 2a, 2d, 2g, 2i, 2t exhibited potent activities on WM3629 cell lines (IC(50)=0.56-0.86 microM). Especially, 2t was found to be a potent and selective C-Raf inhibitor, showing a possibility as melanoma therapeutics.
Bioorganic & medicinal chemistry letters 06/2010; 20(12):3805-8. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The synthesis of a novel series of pyrimidin-4-yl-1H-imidazol-2-yl derivatives 7, 8, 9 and their antiproliferative activities against A375P human melanoma cell line and WM3629 cell line were described. Most compounds showed superior antiproliferative activities compared to Sorafenib, the well-known RAF inhibitor. Among them, 7a exhibited potent activities on both cell lines (IC(50)=0.62 and 4.49muM, respectively) and turned out to be a selective and potent CRAF inhibitor.
Bioorganic & medicinal chemistry letters 01/2010; 20(5):1573-7. · 2.65 Impact Factor
-
Myung-Ho Jung, Hwan Kim,
Won-Kyoung Choi,
Mohammed I El-Gamal,
Jin-Hun Park,
Kyung Ho Yoo,
Tae Bo Sim,
So Ha Lee,
Daejin Baek,
Jung-Mi Hah,
Jung-Hyuck Cho,
Chang-Hyun Oh
[show abstract]
[hide abstract]
ABSTRACT: Synthesis of a new series of diarylureas and amides having pyrrolo[2,3-d]pyrimidine scaffold is described. Their in vitro antiproliferative activities against A375 human melanoma cell line and HS 27 fibroblast cell line were tested and the effect of substituents on pyrrolo[2,3-d]pyrimidine was investigated. The newly synthesized compounds, except N-acetyl derivatives (Id, Ie, and Im), generally showed superior or similar activity against A375 to Sorafenib. Among all of these derivatives, compounds Iq and Ir having imidazole and morpholine moieties, respectively, showed the most potent antiproliferative activity against A375.
Bioorganic & medicinal chemistry letters 12/2009; 19(23):6538-43. · 2.65 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The synthesis of a novel series of aminoquinoline derivatives 1a-p and their antiproliferative activities against A375 human melanoma cell line were described. Most compounds showed superior antiproliferative activities to Sorafenib as a reference compound. Among them, quinolinyloxymethylphenyl compounds 1k and 1l exhibited potent activities (IC(50)=0.77 and 0.79microM, respectively) and excellent selectivity against melanoma and fibroblast cell lines.
Bioorganic & medicinal chemistry letters 08/2009; 19(13):3517-20. · 2.65 Impact Factor
-
Hee Jin Kim,
Myung-Ho Jung, Hwan Kim,
Mohammed I El-Gamal,
Tae Bo Sim,
So Ha Lee,
Jun Hee Hong,
Jung-Mi Hah,
Jung-Hyuck Cho,
Jung Hoon Choi,
Kyung Ho Yoo,
Chang-Hyun Oh
[show abstract]
[hide abstract]
ABSTRACT: Synthesis of a new series of diarylureas and amides having pyrrolo[3,2-b]pyridine scaffold is described. Their in vitro antiproliferative activity against human melanoma cell line A375 and HS 27 human fibroblast cell line was tested and the effect of substituents on the pyrrolo[3,2-b]pyridine was investigated. The newly synthesized compounds, except meta-substituted derivatives (Ij-k and Iv-w), generally showed superior or similar activity against A375 to Sorafenib. Among all of these derivatives, compounds Ir and It having 5-benzylamide substituted 4'-amide moieties showed the most potent antiproliferative activity against A375.
Bioorganic & medicinal chemistry letters 08/2009; 20(1):413-7. · 2.65 Impact Factor
-
Jinwoo Lee,
Youjin Lee,
Jong Kyu Youn,
Hyon Bin Na,
Taekyung Yu, Hwan Kim,
Sang-Mok Lee,
Yoon-Mo Koo,
Ja Hun Kwak,
Hyun Gyu Park,
Ho Nam Chang,
Misun Hwang,
Je-Geun Park,
Jungbae Kim,
Taeghwan Hyeon
[show abstract]
[hide abstract]
ABSTRACT: Uniformly sized silica-coated magnetic nanoparticles (magnetite@silica) are synthesized in a simple one-pot process using reverse micelles as nanoreactors. The core diameter of the magnetic nanoparticles is easily controlled by adjusting the w value ([polar solvent]/[surfactant]) in the reverse-micelle solution, and the thickness of the silica shell is easily controlled by varying the amount of tetraethyl orthosilicate added after the synthesis of the magnetite cores. Several grams of monodisperse magnetite@silica nanoparticles can be synthesized without going through any size-selection process. When crosslinked enzyme molecules form clusters on the surfaces of the magnetite@silica nanoparticles, the resulting hybrid composites are magnetically separable, highly active, and stable under harsh shaking conditions for more than 15 days. Conversely, covalently attached enzymes on the surface of the magnetite@silica nanoparticles are deactivated under the same conditions.
Small 02/2008; 4(1):143-52. · 8.35 Impact Factor
-
Jinwoo Lee Dr,
Youjin Lee,
Jong Kyu Youn,
Hyon Bin Na,
Taekyung Yu, Hwan Kim,
Sang-Mok Lee Dr,
Yoon-Mo Koo Prof,
Ja Hun Kwak Dr,
Hyun Gyu Park Prof,
Ho Nam Chang Prof,
Misun Hwang,
Je-Geun Park Prof,
Jungbae Kim Dr,
Taeghwan Hyeon Prof
Small 01/2008; 4(1):143 - 152. · 8.35 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although increasing evidence supports the protective role of inhibitor of differentiation and DNA binding-1 (Id-1) against anticancer drug-induced apoptosis, the underlying molecular mechanisms seem to vary depending on the tumor system. Here, we examined the direct role of Id-1 in MCF-7 breast cancer cells by ectopically overexpressing Id-1 under serum-free condition, where the endogenous Id-1 expression was suppressed. Id-1 expression resulted in increased number of viable cells, reduced Bax expression, enhanced Bcl-2 expression, but no change in Bcl-xL expression. The expression of nuclear factor-kappaB (NF-kappaB) was augmented, while those of p53 and IkappaB were reduced. Such changes in p53 and NF-kappaB pathways were also functional, as assessed by real-time polymerase chain reactions and reporter assays of their known downstream targets, p21 and Il-6, as well as Bax and Bcl-2 genes. Finally, Id-1 played a protective role against taxol-induced apoptosis in breast cancer cells as assessed by MTT assay and apoptotic cell count upon taxol treatment (0-200 nM). Reduced Bax expression and enhanced Bcl-2 expression by Id-1 were also noted in the presence of taxol. Taken together, we present a molecular mechanism where Id-1 regulates p53 and NF-kappaB pathways, which in turn regulates Bax and Bcl-2 genes, thus providing a survival advantage under exogenous stress such as serum-free or taxol treatment in MCF-7 breast cancer cells. In this regard, inactivation of Id-1 may provide a potential therapeutic strategy leading to inhibition of breast cancer progression and anti-cancer drug resistance.
Breast Cancer Research and Treatment 01/2008; 112(2):287-96. · 4.43 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Inhibitor of DNA binding 1 (Id-1) has been implicated in tumor angiogenesis by regulating the expression of vascular endothelial growth factor (VEGF), but its molecular mechanism has not been fully understood. Here, we show the cross talk between Id-1 and hypoxia-inducible factor-1alpha (HIF-1alpha), that Id-1 induces VEGF by enhancing the stability and activity of HIF-1alpha in human endothelial and breast cancer cells. Although both the transcript and proteins levels of VEGF were induced by Id-1, only the protein expression of HIF-1alpha was induced without transcriptional changes in both human umbilical endothelial cells and MCF7 breast cancer cells. Such induction of the HIF-1alpha protein did not require de novo protein synthesis but was dependent on the active extracellular response kinase (ERK) pathway. In addition, stability of the HIF-1alpha protein was enhanced in part by the reduced association of the HIF-1alpha protein with von Hippel-Lindau protein in the presence of Id-1. Furthermore, Id-1 enhanced nuclear translocation and the transcriptional activity of HIF-1alpha. Transcriptional activation of HIF-1-dependent promoters was dependent on the active ERK pathway, and the association of HIF-1alpha protein with cyclic AMP-responsive element binding protein was enhanced by Id-1. Finally, Id-1 induced tube formation in human umbilical endothelial cells, which also required active ERK signaling. In conclusion, we provide the molecular mechanism of the cross talk between HIF-1alpha and Id-1, which may play a critical role in tumor angiogenesis.
Molecular Cancer Research 04/2007; 5(4):321-9. · 4.29 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the possibility of novel CaO-SiO2-B2O3 glass-ceramics (CS10B) as a new bone replacement material, we compared the biodegradation and osteoconduction properties of CS10B, hydroxyapatite (HA), and tricalcium phosphate (TCP). Porous CS10B implants were prepared by the polymer sponge method. L5-6 single-level posterolateral spinal fusions were performed on 30 New Zealand white male rabbits. The animals were divided into three groups by implant material: CS10B, HA, and TCP. Radiographs were performed every 2 weeks. All animals were euthanized 12 weeks after surgery. The ratio of the area occupied by the ceramics by final and initial radiographs was calculated using radiomorphometric analysis. Uniaxial tensile strength was determined from seven cases in each group. The ratio of the area occupied by HA (88.7%+/-16.1%) was significantly higher than the others (p<0.005), and the ratio of the area occupied by CS10B (28.2%+/-9.3%) was significantly lower than those of HA and TCP (37%+/-9.6%, p<0.05). The mean values of the tensile strengths of the CS10B (182.7+/-19.9 N) and HA (191.4+/-33.5 N) were significantly higher (p<0.05) than that of TCP (141.1+/-28.2 N). CS10B had a fusion mass tensile strength similar to that of HA. Histological analysis confirmed that CS10B was well incorporated into the fusion mass. These findings suggest that CS10B is a possible bone replacement material.
Journal of Biomedical Materials Research Part A 06/2006; 77(2):362-9. · 2.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We undertook to translate and cross-culturally adapt the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) scale Version 4, an assessment tool for BMT patients' quality of life (QoL). The translation procedure followed the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. At baseline, prior to BMT, 70 allogeneic BMT patients were administered the FACT-BMT scale version 4, as well as the Eastern Cooperative Oncology Group Performance Status Rating (ECOG-PSR), Functional Living Index-Cancer (FLIC), and the Shortened Forms of the Profile of Mood States (BPOMS). Forty seven of these patients were also administered these questionnaires 3 months after BMT, thirty eight patients did 6 months after BMT, and finally 35 patients did 1 year after their BMT. Our results indicated that the FACT-BMT scale Version 4 gave convergent and divergent validity, and had a high internal consistency with its Cronbach's alpha coefficients ranging from 0.64 (EWB at pre-BMT) to 0.94 (the FACT-BMT total). These data support that Korean FACT-BMT is a reliable and valid assessment for measuring the QoL of BMT patients. In the future study, we have to increase the number of cases with larger sample of allogeneic bone marrow transplantation patients, and the duration of long term follow-up should be at least more than 1 year.
Quality of Life Research 05/2006; 15(3):559-64. · 2.30 Impact Factor
-
Heekyoung Chung,
Ji-Youn Jung,
Sung-Dae Cho,
Kyung-A Hong,
Hyun-Jun Kim,
Dong-Hui Shin, Hwan Kim,
Hea Ok Kim,
Dae Hong Shin,
Hyuk Woo Lee,
Lak Shin Jeong,
Gu Kong
[show abstract]
[hide abstract]
ABSTRACT: Agonists to A3 adenosine receptor (A3AR) have been reported to inhibit cell growth and/or induce apoptosis in various tumors. We tested the effect of a novel A3AR agonist generically known as LJ-529 in breast cancer cells. Anchorage-dependent cell growth and in vivo tumor growth were attenuated by LJ-529, independently of its estrogen receptor (ER) alpha status. In addition, apoptosis was induced as evidenced by the activation of caspase-3 and c-poly(ADP)ribose polymerase. Furthermore, the Wnt signaling pathway was down-regulated and p27(kip) was induced by LJ-529. In ER-positive cells, the expression of ER was down-regulated by LJ-529, which might have additionally contributed to attenuated cell proliferation. In ER-negative, c-ErbB2-overexpressing SK-BR-3 cells, the expression of c-ErbB2 and its downstream extracellular signal-regulated kinase pathway were down-regulated by LJ-529. However, such effect of LJ-529 acted independently of its receptor because no A3AR was detected by reverse transcription-PCR in all four cell lines tested. In conclusion, our novel findings open the possibility of LJ-529 as an effective therapeutic agent against both ER-positive and ER-negative breast cancers, particularly against the more aggressive ER-negative, c-ErbB2-overexpressing types.
Molecular Cancer Therapeutics 04/2006; 5(3):685-92. · 5.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In this study, we have translated and cross-culturally adapted the Functional Assessment of Cancer Therapy-Lung (FACT-L) version 4 into Korean, and we have evaluated its reliability and validity. The FACT-L version 4 was translated into Korean following the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology. The psychometric properties of the FACT-L were evaluated in 122 lung cancer patients (mean age, 60.88 years). Pre-testing was performed in 22 patients, and these results indicated good content coverage and overall comprehensibility. In validating the FACT-L version 4, our results indicated high internal consistency of the FACT-L scales, with Cronbach's alpha coefficients ranging from 0.52 to 0.84. The FACT-L also demonstrated good convergent and divergent validity when correlated with the Functional Living Index-Cancer (FLIC) and the shortened forms of the Profile of Mood States (POMS). This reliable and valid instrument can now be used to properly evaluate the quality of life of Korean lung cancer patients.
Quality of Life Research 03/2006; 15(1):161-6. · 2.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the possibility of novel CaO-SiO2-B2O3 glass-ceramics (CS10B) as a new bone replacement material, we compared the biodegradation and osteoconduction properties of CS10B, hydroxyapatite (HA), and tricalcium phosphate (TCP). Porous CS10B implants were prepared by the polymer sponge method. L5–6 single-level posterolateral spinal fusions were performed on 30 New Zealand white male rabbits. The animals were divided into three groups by implant material: CS10B, HA, and TCP. Radiographs were performed every 2 weeks. All animals were euthanized 12 weeks after surgery. The ratio of the area occupied by the ceramics by final and initial radiographs was calculated using radiomorphometric analysis. Uniaxial tensile strength was determined from seven cases in each group. The ratio of the area occupied by HA (88.7% ± 16.1%) was significantly higher than the others (p < 0.005), and the ratio of the area occupied by CS10B (28.2% ± 9.3%) was significantly lower than those of HA and TCP (37% ± 9.6%, p < 0.05). The mean values of the tensile strengths of the CS10B (182.7 ± 19.9 N) and HA (191.4 ± 33.5 N) were significantly higher (p < 0.05) than that of TCP (141.1 ± 28.2 N). CS10B had a fusion mass tensile strength similar to that of HA. Histological analysis confirmed that CS10B was well incorporated into the fusion mass. These findings suggest that CS10B is a possible bone replacement material. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
Journal of Biomedical Materials Research Part A 01/2006; 77A(2):362 - 369. · 2.63 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We undertook to translate and cross-culturally adapt the Functional Assessment of Cancer Therapy-Breast (FACT-B) scale into Korean and to evaluate its reliability and validity. The translation procedure followed the standard Functional Assessment of Chronic Illness Therapy translation methodology. A total of 201 breast cancer patients (mean age, 43.87 years) were studied for psychometric properties of the FACT-B scale. A pre-test of 20 Korean breast cancer patients indicated that the Korean FACT-B scale provided good content coverage and overall comprehensibility. Our results indicated high internal consistency of the FACT-B scale, with Cronbach's alpha coefficients ranging from 0.79 to 0.90. The only exception was the Breast Cancer Scale (BCS), which had a Cronbach's alpha coefficient of 0.67. We can consider that most of the patients in this study had not resumed sexual activity after surgery and found it difficult to comment on this aspect. We also considered that contents of the BCS may have been somewhat heterogeneous. After performing a factor analysis of the BCS data from this study, we identified three factors, accounting 58.8%: psychological distress (5 items, with explained variances of 27.5%), feminine satisfaction (2 items, with explained variances of 17.1%), and physical complaints (2 items, with explained variances of 14.2%). The FACT-B scale also demonstrated good convergent and divergent validity when correlated with the shortened forms of the Profile of Mood States and the Functional Living Index-Cancer (FLIC). We can now evaluate the Quality of Life (QoL) of Korean breast cancer patients using this reliable and valid instrument. Nevertheless our study has the limitation that it did not evaluate the sensitivity to the changes of the patients' QoL in the long term follow-up, and we will supplement it in our further study.
Quality of Life Research 09/2005; 14(6):1627-32. · 2.30 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Porous HA ceramics with 1-dimensional pore channels were fabricated to obtain controllable microstructure. 1-dimensional porous HA was objected to find out the optimum condition of bone ingrowth and also to facilitate the observation of osteocondutive behavior in porous HA. The porous structure was formed by burnt-out of polymeric fibers and the size of pores was determined by the diameter of polymeric fibers. The porosity could be varied by the thickness of HA slurry coated on polymeric fiber and by the thickness of HA tapes inserted between fiber layers. As result, 1-dimensional porous HA ceramics of this study have the uniform interconnection size (50-500 microm) and the linearly open pore structure. The compressive strength of 1-dimensional porous HA was 6-10 MPa similar to that of human cancellous bone. On the in vivo test, oteon-like osteoconduction in pore channel of 1-dimensional porous HA was observed, like what had been found in cortical bones. This osteon-like new bone grew from the surface to the center of pore channels. The 1-dimensional porous HA ceramics prepared in this study were very useful as a model system to observe bone ingrowth in the porous HA implants.
Journal of Materials Science Materials in Medicine 04/2004; 15(3):267-73. · 2.32 Impact Factor
-
Hyun-Seung Ryu,
Jung-Kun Lee,
Jun-Hyuk Seo, Hwan Kim,
Kug Sun Hong,
Deug Joong Kim,
Jae Hyup Lee,
Dong-Ho Lee,
Bong-Soon Chang,
Choon-Ki Lee,
Sung-Soo Chung
[show abstract]
[hide abstract]
ABSTRACT: Novel bioactive and biodegradable glass ceramics with high mechanical strength in the (50-x/2)CaO. SiO(2)--xB(2)O(3) (4.2 < or = x < or = 17.2) system were investigated. The systems consisted of three phases: monoclinic wollastonite, calcium metaborate, and amorphous borosilicate matrix. The glass ceramics containing 4.2 mol% and 8.4 mol% B(2)O(3) showed high bulk density and a dense microstructure. Mechanical strengths of the glass ceramics were higher than those of other bioactive ceramics: high compressive strength (2813 MPa), bending strength of 212 MPa, and fracture toughness of 3.12 MPa. m(1/2). The glass-ceramic formed apatite layer on their surface in the simulated body fluid and showed significant biodegradation. The degree of apatite formation in the glass ceramics depended on the calcium metaborate content and borosilicate glassy matrix. Additional calcium metaborate and borosilicate glassy matrix increased the apatite formation rate on the surface. It might be likely that calcium metaborate causes supersaturation of Ca ions, for its high solubility in SBF and the water-reactive borosilicate glassy matrix formed Sibond;OH groups on the surface to provide nucleation sites for apatite formation. Also, through in vitro test for the biocompatibility of the CaO--SiO(2)--B(2)O(3) glass ceramics, no cytotoxicity of the glass ceramics were found. The results on bioactivity and noncytotoxicity indicated that glass ceramics in the (50-x/2)CaO. SiO(2)--xB(2)O(3) (4.2 < or = x < or = 17.2) system could be useful as a biodegradable bone replacement material.
Journal of Biomedical Materials Research Part A 01/2004; 68(1):79-89. · 2.63 Impact Factor
