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Synthesis and biological evaluation of 2-quinolineacrylamides
Affiliation:1. Department of Medicine, Mackay Medical College, New Taipei City, Taiwan;2. Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan;3. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan;4. Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taiwan;5. Department of Urology, National Yang-Ming University School of Medicine, Taipei, Taiwan;6. Division of Urology, Taipei City Hospital HepingFuyou Branch, Taipei, Taiwan;7. Ph.D Program in Biotechnology Research and Development, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan;1. School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 152 – 160 Pearse Street Trinity College Dublin, Dublin 2, Ireland;2. School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, 152 – 160 Pearse Street Trinity College Dublin, Dublin 2, Ireland;3. School of Biological and Health Sciences, Technology University Dublin, Dublin City Campus, Kevin St., Dublin 8 D08 NF82, Ireland;4. School of Chemistry, Trinity College Dublin, Dublin 2, Ireland;1. Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;2. Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA;1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taiwan;2. TMU Biomedical Commercialization Center, Taipei Medical University, Taiwan;3. Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. School of Pharmacy, National Defense Medical Center, Taipei, Taiwan;5. Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;6. Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan;1. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taiwan;2. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taiwan;3. Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. Graduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;5. School of Pharmacy, National Defense Medical Center, Taipei, Taiwan;6. TMU Biomedical Commercialization Center, Taipei Medical University, Taiwan;7. Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan;8. Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei, Taiwan;1. School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan;2. Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan;3. Taipei Neuroscience Institute, Taipei Medical University, Taiwan;4. Institute of Biotechnology and Pharmaceutical Research, National Health Research Institute, Zhunan Town, Miaoli County, Taiwan;5. TMU Biomedical Commercialization Center, Taipei Medical University, Taiwan
Abstract:A series of C6-substituted N-hydroxy-2-quinolineacrylamides (315), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy-N-hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors.
Keywords:Histone deacetylase  2-Quinolineacrylamide  Ullmann reaction
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