The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Lijun Tang - One of the best experts on this subject based on the ideXlab platform.
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fluorescence relay enhancement sequential recognition of cu2 and cn by a new Quinazoline Derivative
Sensors and Actuators B-chemical, 2013Co-Authors: Lijun Tang, Pei Zhou, Keli Zhong, Shuhua HouAbstract:Abstract Sequential recognition of Cu 2+ and CN − by a new benzimidazole-containing Quinazoline based probe (1) has been achieved. Probe 1 exhibits highly selective and sensitive fluorescence “off-on” recognition properties to Cu 2+ in CH 3 CH 2 OH/H 2 O (1/1, v/v, HEPES 20 mM, pH 7.0) solution with a 2:1 binding stoichiometry. The in situ prepared 1-Cu 2+ complex solution displays high selectivity to CN − through fluorescence relay enhancement. This Cu 2+ and CN − sequential recognition via fluorescence relay enhancement make probe 1 has a potential utility for Cu 2+ and CN − detection in aqueous media.
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a new benzimidazole based Quinazoline Derivative for highly selective sequential recognition of cu2 and cn
Tetrahedron Letters, 2013Co-Authors: Lijun Tang, Nannan Wang, Qiang Zhang, Jiaojiao Guo, Raju NandhakumarAbstract:Abstract A new benzimidazole-based Quinazoline Derivative (1) has been designed and synthesized as a fluorescent probe. Probe 1 exhibits high selectivity and sensitivity to Cu2+ as fluorescence ‘on–off’ behavior in HEPES-buffered CH3OH/H2O (1:1, v/v, pH = 7.0) solution. The in situ formed 1-Cu2+ complex is further utilized to sense the cyanide ions with high selectivity and fluorescence enhancement performance.
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A new benzimidazole-based Quinazoline Derivative for highly selective sequential recognition of Cu2+ and CN−
Tetrahedron Letters, 2013Co-Authors: Lijun Tang, Nannan Wang, Qiang Zhang, Jiaojiao Guo, Raju NandhakumarAbstract:Abstract A new benzimidazole-based Quinazoline Derivative (1) has been designed and synthesized as a fluorescent probe. Probe 1 exhibits high selectivity and sensitivity to Cu2+ as fluorescence ‘on–off’ behavior in HEPES-buffered CH3OH/H2O (1:1, v/v, pH = 7.0) solution. The in situ formed 1-Cu2+ complex is further utilized to sense the cyanide ions with high selectivity and fluorescence enhancement performance.
Raju Nandhakumar - One of the best experts on this subject based on the ideXlab platform.
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a new benzimidazole based Quinazoline Derivative for highly selective sequential recognition of cu2 and cn
Tetrahedron Letters, 2013Co-Authors: Lijun Tang, Nannan Wang, Qiang Zhang, Jiaojiao Guo, Raju NandhakumarAbstract:Abstract A new benzimidazole-based Quinazoline Derivative (1) has been designed and synthesized as a fluorescent probe. Probe 1 exhibits high selectivity and sensitivity to Cu2+ as fluorescence ‘on–off’ behavior in HEPES-buffered CH3OH/H2O (1:1, v/v, pH = 7.0) solution. The in situ formed 1-Cu2+ complex is further utilized to sense the cyanide ions with high selectivity and fluorescence enhancement performance.
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A new benzimidazole-based Quinazoline Derivative for highly selective sequential recognition of Cu2+ and CN−
Tetrahedron Letters, 2013Co-Authors: Lijun Tang, Nannan Wang, Qiang Zhang, Jiaojiao Guo, Raju NandhakumarAbstract:Abstract A new benzimidazole-based Quinazoline Derivative (1) has been designed and synthesized as a fluorescent probe. Probe 1 exhibits high selectivity and sensitivity to Cu2+ as fluorescence ‘on–off’ behavior in HEPES-buffered CH3OH/H2O (1:1, v/v, pH = 7.0) solution. The in situ formed 1-Cu2+ complex is further utilized to sense the cyanide ions with high selectivity and fluorescence enhancement performance.
Naoyuki Kanzaki - One of the best experts on this subject based on the ideXlab platform.
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discovery of novel highly potent and selective matrix metalloproteinase mmp 13 inhibitors with a 1 2 4 triazol 3 yl moiety as a zinc binding group using a structure based design approach
Journal of Medicinal Chemistry, 2017Co-Authors: Hiroshi Nara, Akira Kaieda, Kenjiro Sato, Takako Naito, Hideyuki Mototani, Hideyuki Oki, Yoshio Yamamoto, Haruhiko Kuno, Takashi Santou, Naoyuki KanzakiAbstract:On the basis of a superposition study of X-ray crystal structures of complexes of Quinazoline Derivative 1 and triazole Derivative 2 with matrix metalloproteinase (MMP)-13 catalytic domain, a novel series of fused pyrimidine compounds which possess a 1,2,4-triazol-3-yl group as a zinc binding group (ZBG) was designed. Among the herein described and evaluated compounds, 31f exhibited excellent potency for MMP-13 (IC50 = 0.036 nM) and selectivities (greater than 1,500-fold) over other MMPs (MMP-1, -2, -3, -7, -8, -9, -10, and -14) and tumor necrosis factor-α converting enzyme (TACE). Furthermore, the inhibitor was shown to protect bovine nasal cartilage explants against degradation induced by interleukin-1 and oncostatin M. In this article, we report the discovery of extremely potent, highly selective, and orally bioavailable fused pyrimidine Derivatives that possess a 1,2,4-triazol-3-yl group as a novel ZBG for selective MMP-13 inhibition.
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Discovery of Novel, Highly Potent, and Selective Matrix Metalloproteinase (MMP)-13 Inhibitors with a 1,2,4-Triazol-3-yl Moiety as a Zinc Binding Group Using a Structure-Based Design Approach
2016Co-Authors: Hiroshi Nara, Akira Kaieda, Kenjiro Sato, Takako Naito, Hideyuki Mototani, Hideyuki Oki, Yoshio Yamamoto, Haruhiko Kuno, Takashi Santou, Naoyuki KanzakiAbstract:On the basis of a superposition study of X-ray crystal structures of complexes of Quinazoline Derivative 1 and triazole Derivative 2 with matrix metalloproteinase (MMP)-13 catalytic domain, a novel series of fused pyrimidine compounds which possess a 1,2,4-triazol-3-yl group as a zinc binding group (ZBG) was designed. Among the herein described and evaluated compounds, 31f exhibited excellent potency for MMP-13 (IC50 = 0.036 nM) and selectivities (greater than 1,500-fold) over other MMPs (MMP-1, -2, -3, -7, -8, -9, -10, and -14) and tumor necrosis factor-α converting enzyme (TACE). Furthermore, the inhibitor was shown to protect bovine nasal cartilage explants against degradation induced by interleukin-1 and oncostatin M. In this article, we report the discovery of extremely potent, highly selective, and orally bioavailable fused pyrimidine Derivatives that possess a 1,2,4-triazol-3-yl group as a novel ZBG for selective MMP-13 inhibition
Zhi-shu Huang - One of the best experts on this subject based on the ideXlab platform.
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Discovery of Small Molecules for Repressing Cap-Independent Translation of Human Vascular Endothelial Growth Factor (hVEGF) as Novel Antitumor Agents
2017Co-Authors: Shi-ke Wang, Jia-heng Tan, Qi Zhang, Xiao-qin Wang, Guo-tao Kuang, Shu-ling Lin, Hui-yun Liu, Zhi-shu HuangAbstract:Angiogenesis is important in tumorigenesis and tumor progression. Human vascular endothelial growth factor (hVEGF) is an angiogenic growth factor that plays a crucial role in tumor progression. The G-rich region within the 5′-untranslated regions (5′-UTR) of hVEGF-A mRNA can form a “switchable” RNA G-quadruplex structure that is essential for a cap-independent translation initiation. We screened our small-molecule library for binders of this G-tract. One novel Quinazoline Derivative, compound 1, showed a significant specific interaction with the G-tract and destabilized the G-quadruplex structure. The results of cellular experiments revealed that compound 1 down-regulated hVEGF-A translation and significantly impeded tumor cells migration. We also found that compound 1 exhibited tumor-inhibiting activity in MCF-7 xenograft tumors, which might be related to its ability to reduce hVEGF expression. These findings present a new strategy of hVEGF-A translational control in which small molecules interact with G-quadruplex structure in the 5′UTR
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Mechanistic studies on the anticancer activity of 2,4-disubstituted Quinazoline Derivative.
Biochimica et biophysica acta, 2014Co-Authors: Huaqin Zheng, Jun Qiu, Siqi Chen, Jinggong Liu, Jia-heng Tan, Zhi-shu HuangAbstract:Abstract Background Accelerated proliferation of solid tumor and hematologic cancer cells is related to accelerated transcription of ribosomal DNA by the RNA polymerase I to produce elevated level of ribosomal RNA. Therefore, down-regulation of RNA polymerase I transcription in cancer cells is an important anticancer therapeutic strategy. Methods A variety of methods were used, including cloning, expression and purification of protein, electrophoretic mobility shift assay (EMSA), circular dichroic (CD) spectroscopy, CD-melting, isothermal titration calorimetry (ITC), chromatin immunoprecipitation (Ch-IP), RNA interference, RT-PCR, Western blot, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell assay. Results Our results showed that 2,4-disubstituted Quinazoline Derivative Sysu12d could down-regulate c-myc through stabilization of c-myc promoter G-quadruplex, resulting in down-regulation of nucleolin expression. Sysu12d could also disrupt nucleolin/G-quadruplex complex. Both of the above contributed to the down-regulation of ribosomal RNA synthesis, followed by activation of p53 and then cancer cell apoptosis. Conclusions These mechanistic studies set up the basis for further development of Sysu12d as a new type of lead compound for cancer treatment. General significance 2,4-Disubstituted Quinazoline Derivatives may have multi-functional effect for cancer treatment.
Giampaolo Tortora - One of the best experts on this subject based on the ideXlab platform.
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a novel approach in the treatment of cancer targeting the epidermal growth factor receptor
Clinical Cancer Research, 2001Co-Authors: Fortunato Ciardiello, Giampaolo TortoraAbstract:The epidermal growth factor receptor (EGFR) autocrine pathway contributes to a number of processes important to cancer development and progression, including cell proliferation, apoptosis, angiogenesis, and metastatic spread. The critical role the EGFR plays in cancer has led to an extensive search for selective inhibitors of the EGFR signaling pathway. The results of a large body of preclinical studies and the early clinical trials thus far conducted suggest that targeting the EGFR could represent a significant contribution to cancer therapy. A variety of different approaches are currently being used to target the EGFR. The most promising strategies in clinical development include monoclonal antibodies to prevent ligand binding and small molecule inhibitors of the tyrosine kinase enzymatic activity to inhibit autophosphorylation and downstream intracellular signaling. At least five blocking monoclonal antibodies have been developed against the EGFR. Among these, IMC-225 is a chimeric human-mouse monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy to enter clinical evaluation in cancer patients in Phase II and III studies, alone or in combination with conventional therapies, such as radiotherapy and chemotherapy. A number of small molecule inhibitors of the EGFR tyrosine kinase enzymatic activity is also in development. OSI-774 and ZD1839 (Iressa) are currently in Phase II and III development, respectively. ZD1839, a p.o. active, selective Quinazoline Derivative has demonstrated promising in vitro and in vivo antitumor activity. Preliminary results from Phase I and II trials in patients with advanced disease demonstrate that ZD1839 and OSI-774 have an acceptable tolerability profile and promising clinical efficacy in patients with a variety of tumor types. This mini-review describes the EGFR inhibitors in clinical development.
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antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by zd 1839 iressa an epidermal growth factor receptor selective tyrosine kinase inhibitor
Clinical Cancer Research, 2000Co-Authors: Fortunato Ciardiello, R Caputo, Roberto Bianco, Vincenzo Damiano, G Pomatico, Sabino De Placido, Raffaele A Bianco, Giampaolo TortoraAbstract:Transforming growth factor α (TGF-α) is an autocrine growth factor for human cancer. Overexpression of TGF-α and its specific receptor, the epidermal growth factor receptor (EGFR), is associated with aggressive disease and poor prognosis. The EGFR has been proposed as a target for anticancer therapy. Compounds that block ligand-induced EGFR activation have been developed. ZD-1839 (Iressa) is a p.o.-active, Quinazoline Derivative that selectively inhibits the EGFR tyrosine kinase and is under clinical development in cancer patients. The antiproliferative activity of ZD-1839 alone or in combination with cytotoxic drugs differing in mechanism(s) of action, such as cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, doxorubicin, etoposide, topotecan, and raltitrexed, was evaluated in human ovarian (OVCAR-3), breast (ZR-75–1, MCF-10A ras ), and colon cancer (GEO) cells that coexpress EGFR and TGF-α. ZD-1839 inhibited colony formation in soft agar in a dose-dependent manner in all cancer cell lines. The antiproliferative effect was mainly cytostatic. However, treatment with higher doses resulted in a 2–4-fold increase in apoptosis. A dose-dependent supra-additive increase in growth inhibition was observed when cancer cells were treated with each cytotoxic drug and ZD-1839. The combined treatment markedly enhanced apoptotic cell death induced by single-agent treatment. ZD-1839 treatment of nude mice bearing established human GEO colon cancer xenografts revealed a reversible dose-dependent inhibition of tumor growth because GEO tumors resumed the growth rate of controls at the end of the treatment. In contrast, the combined treatment with a cytotoxic agent, such as topotecan, raltitrexed, or paclitaxel, and ZD-1839 produced tumor growth arrest in all mice. Tumors grew slowly for approximately 4–8 weeks after the end of treatment, when they finally resumed a growth rate similar to controls. GEO tumors reached a size not compatible with normal life in all control mice within 4–6 weeks and in all single agent-treated mice within 6–8 weeks after GEO cell injection. In contrast, 50% of mice treated with ZD-1839 plus topotecan, raltitrexed, or paclitaxel were still alive 10, 12, and 15 weeks after cancer cell injection, respectively. These results demonstrate the antitumor effect of this EGFR-selective tyrosine kinase inhibitor and provide a rationale for its clinical evaluation in combination with cytotoxic drugs.
