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Kyeong Lee,
Soo Hyun Cho,
Jee Hyun Lee,
Jail Goo,
Sung Yoon Lee,
Shanthaveerappa K Boovanahalli,
Siok Koon Yeo,
Sung-Joon Lee,
Young Kook Kim,
Dong Hee Kim,
Yongseok Choi, Gyu-Yong Song
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ABSTRACT: We report a new series of naphthoquinone derivatives as potent ACAT inhibitors, which were obtained through structural variations of previously disclosed lead 1. Several analogs represented by 3i-l, 4k-m, 6a-n, 7a, and 7i demonstrated potent human macrophage ACAT inhibitory activity by a cell-based reporter assay with human HepG2 cell lines. In particular, compounds 4l and 6j emerged as highly potent inhibitors, exhibiting significantly high inhibitory potencies with IC(50) values of 0.44 μM and 0.6 μM, respectively. Moreover, compound 4l significantly reduced the accumulation of cellular cholesterol in HepG2 cell lines.
European journal of medicinal chemistry 01/2013; 62C:515-525. · 3.27 Impact Factor
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Kyeong Lee,
Minkyoung Kim,
Boah Lee,
Jail Goo,
Jiyoung Kim,
Ravi Naik,
Jee Hee Seo,
Mun Ock Kim,
Youngjoo Byun, Gyu-Yong Song,
Hyun Sun Lee,
Yongseok Choi
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ABSTRACT: A series of indolyl acrylamide derivatives was synthesized as potential diacylglycerol acyltransferase (DGAT) inhibitors. Furfurylamine containing indolyl acrylamide derivative exhibited the most potent DGAT inhibitory activity using microsomes prepared from rat liver. Further evaluation against human DGAT-1 and DGAT-2 identified indolyl acrylamide analogues as selective inhibitors against human DGAT-2. In addition, the most potent compound inhibited triglyceride synthesis dose-dependently in HepG2 cell lines.
Organic & Biomolecular Chemistry 12/2012; · 3.70 Impact Factor
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ABSTRACT: In this study, we synthesized a novel chemical, (E)-2-(3,4-dimethoxyphenyl)-4-oxo-4H-chromen-7-yl-3-(3,4-dimethoxyphenyl) acrylate (CSH) and investigated the effect of CSH on atopic dermatitis (AD) by evaluating the anti-inflammatory effect of CSH on immune cells in vitro and on atopic dermatitis-like lesions in vivo.
Human monocytic THP-1 cells and human eosinophilic EoL-1 cells were treated with house dust mite extract in the absence and presence of CSH. Nc/Nga mice were sensitized to 2,4-dinitrochlorobenzne (DNCB) for 5weeks and then orally and dorsally administered with CSH or dexamethasone for 3weeks.
CSH inhibited the secretion of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6 and IL-8 due to house dust mite extract in THP-1 cells. CSH also suppressed the secretion of MCP-1 and IL-8 in EoL-1 cells. In vivo, the skin severity score decreased after CSH treatment as compared to the control group. CSH suppressed the inflammatory cell infiltration into the dermis and thickened the epidermis. CSH reduced serum IgE level as compared to the control group. The levels of IL-4, IL-5, IL-13 and eotaxin in mouse splenocytes increased after treatment with concanavalin A and the increase of the cytokines was decreased by pre-treatment with CSH. The inhibitory effects of CSH on atopic lesions of DNCB-treated Nc/Nga mice were similar to those of dexamethasone, despite differing degrees depending on results evaluated in this study.
These results may contribute to the development of a therapeutic drug for the treatment of AD.
Life sciences 07/2012; 91(9-10):338-44. · 2.56 Impact Factor
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ABSTRACT: Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.
Cell Biology International 07/2012; 36(7):683-8. · 1.48 Impact Factor
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ABSTRACT: Ginseng leaves and flowers have been known to be rich in various ginsenosides. The aim of present study is to screen the effect
of 34 ginsenosides from ginseng leaves and flowers on interlukin (IL)-12 production in bone marrow-derived dendritic cells
induced by lipopolysaccharide (LPS). Noticeably, floralginsenoside Kc (5), floralginsenoside J (26), and ginsenoside I (33) exhibited particularly inhibitory effect on LPS-induced IL-12 production with IC50 values of 16.3, 25.8, and 6.7 μM, respectively. In addition, floralginsenoside Kc (5) suppressed significantly LPS-stimulated
IL-6 and tumor necrosis factor-α (TNF-α) production. These results warrant further studies concerning potential of saponin
extracts of Panax ginseng leaves and flowers for medicinal foods.
Keywordsinterleukin-12-
Panax ginseng
-ginsenoside-bone marrow-derived dendritic cell
Food science and biotechnology 04/2012; 19(4):1119-1122. · 0.49 Impact Factor
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ABSTRACT: This study investigates phenolic components from the Panax ginseng C.A. Meyer leaves led to the isolation of 3 flavonoids (1–3). Their structures were characterized on the basis of physicochemical properties, nuclear magnetic resonance (NMR) spectra,
electron spray ionization-mass spectrometry (ESI-MS) data, and comparison with those in the literature. Of them, sophoraflavonoloside
(2) and prunin (3) were found to inhibit the growth of HL-60 human leukemia cells with IC50 in values of 29.8 and 21.4 μM by the induction of apoptosis.
Keywords
Panax ginseng
-Araliaceae-flavonoid-cytotoxic activity-HL-60 cell-apoptosis
Food science and biotechnology 04/2012; 19(1):271-274. · 0.49 Impact Factor
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ABSTRACT: The antioxidant activity of saponins isolated from Platycodon grandiflorum (PG; Balloon flower) was determined using the total oxidant-scavenging capacity (TOSC) assay. Platycodigenin, polygalacic acid, platycodin D, platycoside E and deapioplatycoside E were isolated and their structures were characterised based on their physical and spectral properties and by comparison of these results with similar data in the literature. Platycodin D showed the greatest TOSC value against peroxyl radicals, followed (in decreasing order) by polygalacic acid, platycodigenin, deapioplatycosides E and platycoside E. Although the TOSC value of the saponins against peroxyl radicals was less than that of glutathione (GSH) and Trolox used as positive controls. However, TOSC value of platycodigenin, deapioplatycoside E, platycodin D or platycoside E against peroxynitrite was 2.35-, 1.27-, 1.02- or 0.75-fold of GSH, respectively, while polygalacic acid exhibited no scavenging capacity of peroxynitrites. These results suggest importance of the presence of hydroxyl group at carbon 24 in platycodigenin in peroxynitrite scavenging. As the number of attached sugar residues in the saponin glycosides is increased, the scavenging capacity of peroxyl radical, but not peroxynitrite was significantly decreased. These results showed that PG saponins have potent antioxidant activities, which is different according to the structure of aglycones and the number of attached sugar residues.
Food Chemistry. 04/2012; 132:333-337.
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ABSTRACT: A new lupane-triterpene, 3β-cis-feruloyloxy-16β-hydroxylup-20(29)-ene (1) were isolated from the ethyl acetate extract of Panax ginseng seeds along with the known compound, 3β-transferuloyloxy-16β-hydroxylup-20(29)-ene (2). Compound 2 was isolated from this plant for the first time. Their chemical structures were determined by mass spectroscopy and one-dimensional and two-dimensional magnetic resonance spectra. The bioactive effects of these compounds on TNF-α-induced NF-κB transcription were evaluated in transfected HepG2 cells. Effects on the expression of NF-κB target genes were also examined using a reverse transcription-polymerase chain reaction. Both compounds 1 and 2 were inhibited NF-κB activity in HepG2 cells by decreasing the cellular concentrations of inflammatory factors iNOS and COX2.
Archives of Pharmacal Research 03/2012; 35(4):647-51. · 1.59 Impact Factor
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ABSTRACT: Aberrant accumulation of intracellular β-catenin is a well recognized characteristic of several cancers, including prostate, colon, and liver cancers, and is a potential target for development of anticancer therapeutics. Here, we used cell-based small molecule screening to identify CGK062 as an inhibitor of Wnt/β-catenin signaling. CGK062 promoted protein kinase Cα (PKCα)-mediated phosphorylation of β-catenin at Ser33/Ser37, marking it for proteasomal degradation. This reduced intracellular β-catenin levels and consequently antagonized β-catenin response transcription (CRT). Pharmacological inhibition or depletion of PKCα abrogated CGK062-mediated phosphorylation and degradation of β-catenin. In addition, CGK062 repressed the expression of the genes encoding cyclin D1, c-myc, and axin-2, β-catenin target genes, and thus inhibited the growth of CRT-positive cancer cells. Furthermore, treatment of nude mice bearing PC3 xenograft tumors with CGK062 at doses of 50 mg/kg and 100 mg/kg (i.p.) significantly suppressed tumor growth. Our findings suggest that CGK062 exerts its anticancer activity by promoting PKCα-mediated β-catenin phosphorylation/degradation. Therefore, CGK062 has significant therapeutic potential for the treatment of CRT-positive cancers.
PLoS ONE 01/2012; 7(10):e46697. · 4.09 Impact Factor
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ABSTRACT: Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G(0)/G(1) phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLCγ inhibitor, increased the proportion of cells in the G(0)/G(1) phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G(0)/G(1) phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.
Biochemical and Biophysical Research Communications 07/2011; 411(1):213-8. · 2.48 Impact Factor
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ABSTRACT: Interleukin-12, a heterodimeric cytokine comprising p40 and p35 subunits, plays an essential role in the regulating the differentiation of Th cells, which establish and maximize the capabilities of the immune system. The aim of present study is to screen the effect of 21 ginsenosides from steamed ginseng-leaves and flowers on IL-12 production in bone marrow-derived dendritic cells induced by lipopolysaccharide. Noticeably, ginsenoside Rg(6) (12) and ginsenoside F(4) (13) exhibited particularly inhibitory effect on LPS-induced IL-12 production with the inhibition values of 80 and 82%; and ginsenoside ST(1) (4), ginsenoside SL(2) (8), ginsenoside SL(3) (9), ginsenoside Rh(3) (14), ginsenoside Rk(2) (15), and ginsenoside Rs(4) (18) showed moderate effects with inhibition rates of 63, 65, 67, 68, 71, 73, and 67%, respectively. These results warrant further studies concerning potential of saponin extracts of steamed ginseng-leaves and flowers for medicinal uses.
Archives of Pharmacal Research 04/2011; 34(4):681-5. · 1.59 Impact Factor
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ABSTRACT: Age-related changes in hepatic expression and activity of cytochrome P450 (CYP) were investigated in male rats aged 3 (weanling), 12 (young), 26 (adult), and 104 (old) weeks. Levels of microsomal protein, total CYP, and cytochrome b(5) increased fully after puberty. CYP1A1 was detected only in 3-week-old rats, and CYP1A2, CYP2B1, and CYP2E1 were maximally expressed at 3 weeks but decreased at 12 and 26 weeks. CYP2C11 and CYP3A2 increased markedly after puberty and decreased with aging. Ethoxyresorufin-O-deethylase, methoxyresorufin-O-demethylase, pentoxyresorufin-O-depenthylase, and p-nitrophenol hydroxylase activities were at their highest in 3-week-old rats, and midazolam hydroxylase activity was at a maximum in 12-week-old rats but decreased with aging. The present results show that increasing age caused significant alterations in hepatic expression/activity of CYP isoforms in an isoform-specific manner. These results suggest that age-related changes in hepatic CYP isoforms may be an important factor for deciding the efficacy and safety of xenobiotics.
Archive für Toxikologie 12/2010; 84(12):939-46. · 4.67 Impact Factor
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ABSTRACT: We report the synthesis of a novel series of highly potent melanin inhibitors which were obtained through structural modification of an anticancer compound S-(+)-decursinol. The in vitro inhibitory potencies of the newly synthesized compounds were evaluated against α-MSH induced melanin production in B16 murine melanoma cells. Among the compounds evaluated, compounds 2, 3, 6b, 7a, 7b, 8a and 8b emerged as highly potent inhibitors of melanin production. Besides, these compounds demonstrated significantly low cytotoxicity.
European journal of medicinal chemistry 09/2010; 45(12):5567-75. · 3.27 Impact Factor
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ABSTRACT: Three new dammarane-type glycosides, named ginsenosides SL(1)-SL(3) (1-3), and eleven known compounds (4-14) were isolated from the heat-processed leaves of Panax ginseng. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Cytotoxic-activity testing of compounds 1-14 against human leukemia HL-60 cells showed that ginsenosides Rh(3) (11) and Rk(2) (12) exhibited potent effects with IC(50) values of 0.8 and 0.9 microM. In addition, ginsenosides SL(3) (3), 20S-Rg(2) (7), F(4) (10), 20S-Rh(2) (13) displayed strong activity with IC(50) values of 9.0, 9.0, 7.5, and 8.2 microM, respectively. This is the first report on chemical components of the steamed ginseng leaves.
Chemical & pharmaceutical bulletin 08/2010; 58(8):1111-5. · 1.70 Impact Factor
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ABSTRACT: In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that 1 effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with 1 were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with 1, but that Akt was unchanged. Therefore, the effects of 1 on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by 1. Finally, MITF down-regulation by 1 was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.
Journal of Natural Products 04/2010; 73(5):797-800. · 3.13 Impact Factor
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Soo Jin Oh,
Jooyoung Chae,
Hongmei Zhu,
Tran Thi Hien,
Kiho Lee,
Hwan Mook Kim,
Keon Wook Kang, Gyu Yong Song,
Jong Seong Kang,
Bong-Hee Kim,
Kwang-il Kwon,
Sang Kyum Kim
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ABSTRACT: Retroviral gene transfer technology is frequently used to establish stable transgenic cell lines. However, no studies to date have evaluated antioxidant defense systems in cells infected with retroviral particles. In the present study, we examined the effects of retroviral infection on antioxidant defense systems using H4IIE cells infected with a retrovirus that overexpresses green fluorescent protein (retro-H4IIE cells). Total oxyradical scavenging capacity and glutathione (GSH), malondialdehyde, and peroxide levels were not significantly altered in retro-H4IIE cells; however, retro-H4IIE cells showed a higher resistance against cytotoxicity, GSH depletion, and malondialdehyde elevation under H(2)O(2)-induced oxidative stress conditions. Immunoblot analysis showed that alpha-class GSH S-transferase (GST) was increased 2.5-fold in retro-H4IIE cells as compared with H4IIE cells; however, catalase, GSH peroxidase-1, peroxiredoxin-1, and thioredoxin-1 remained unaltered or slightly decreased. l-Buthionine-(S,R)-sulfoximine, a GSH synthesis inhibitor, and 1-chloro-2,4-dinitrobenzene, a GST substrate and competitive inhibitor, decreased the difference in H(2)O(2) responses between the two cell types. These results support the hypothesis that the resistance of retro-H4IIE cells to H(2)O(2) can be attributed to an increase in alpha-class GST expression, as levels of GSH and GSH peroxidase-1 were not altered. The present study suggests that antioxidant enzyme expression may change during the establishment of stable transformed cell lines using retroviral techniques.
Toxicology in Vitro 03/2010; 24(4):1105-10. · 2.78 Impact Factor
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Nguyen Huu Tung, Gyu Yong Song,
Nguyen Xuan Nhiem,
Yan Ding,
Bui Huu Tai,
Long Guo Jin,
Chae-Moon Lim,
Jin Won Hyun,
Chun Jung Park,
Hee Kyoung Kang,
Young Ho Kim
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ABSTRACT: Korean ginseng (Panax ginseng C.A. Meyer) has been extensively used as a functional food for thousands of years. This study with the aim to evaluate the potential of P. ginseng flower components as a functional food with medicinal properties resulted in the identification of three new dammarane-type saponins, named floralginsenosides Ka-Kc (1-3), along with seventeen known ones (4-20). Their structures were elucidated on the basis of chemical and spectroscopic methods, and their antioxidant activities were evaluated by the intracellular ROS radical scavenging DCF-DA assay. Among them, floralginsenoside Ka (1) displayed potent scavenging activity with the inhibition value of 64% at 10 microM; and ginsenoside Rb(1) (13), floralginsenoside Kc (3), floralginsenoside Kb (2), vinaginsenoside R(9) (11), majoroside F(1) (12), ginsenoside I (17), and ginsenoside II (18) showed moderate scavenging capacity with the inhibition rate of 28, 33, 35, 35, 35, 38, and 38% at 10 microM, respectively. These results warrant further studies concerning the potential of saponin extracts of P. ginseng flowers for functional foods.
Journal of Agricultural and Food Chemistry 01/2010; 58(2):868-74. · 2.82 Impact Factor
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ABSTRACT: Two new dammarane-type saponins, named ginsenoside Ki (1a) and ginsenoside Km (1b), along with 15 known ones (2-16), were isolated from the leaves of Panax ginseng. Their structures were elucidated on the basis of chemical and spectroscopic methods.
Chemical & pharmaceutical bulletin 12/2009; 57(12):1412-4. · 1.70 Impact Factor
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Hyuk Choi,
Jungsug Gwak,
Munju Cho,
Min-Jung Ryu,
Jee-Hyun Lee,
Sang Kyum Kim,
Young Ho Kim,
Gye Won Lee,
Mi-Young Yun,
Nguyen Manh Cuong,
Jae-Gook Shin, Gyu-Yong Song,
Sangtaek Oh
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ABSTRACT: Molecular lesions in Wnt/beta-catenin signaling and subsequent up-regulation of beta-catenin response transcription (CRT) occur frequently during the development of colon cancer. To identify small molecules that suppress CRT, we screened natural compounds in a cell-based assay for detection of TOPFalsh reporter activity. Murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa, antagonized CRT that was stimulated by Wnt3a-conditioned medium (Wnt3a-CM) or LiCl, an inhibitor of glycogen synthase kinase-3beta (GSK-3beta), and promoted the degradation of intracellular beta-catenin without altering its N-terminal phosphorylation at the Ser33/37 residues, marking it for proteasomal degradation, or the expression of Siah-1, an E3 ubiquitin ligase. Murrayafoline A repressed the expression of cyclin D1 and c-myc, which is known beta-catenin/T cell factor (TCF)-dependent genes and thus inhibited the proliferation of various colon cancer cells. These findings indicate that murrayafoline A may be a potential chemotherapeutic agent for use in the treatment of colon cancer.
Biochemical and Biophysical Research Communications 12/2009; 391(1):915-20. · 2.48 Impact Factor
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ABSTRACT: Six dammarane-type saponins, including three new compounds, floralginsenosides Ta-Tc (1-3), and three known, floralginsenoside Td (4), ginsenoside F(1) (5), and ginsenoside F(5) (6), were isolated from the flower buds of Panax ginseng. Floralginsenoside Td (4) was first isolated from natural plant sources. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Compounds 1, 5, and 6 showed cytotoxic activities towards the HL-60 human leukemia cell line with respective IC(50) values of 36.3, 23.2, and 62.4microM. In addition, after the HL-60 cells were treated with these compounds, several apoptosis events, including chromatin condensation and increase in the population of sub-G1 hypodiploid cells, were observed.
Bioorganic & medicinal chemistry letters 10/2009; 20(1):309-14. · 2.65 Impact Factor
