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Anti-tumor activity evaluation of novel tubulin and HDAC dual-targeting inhibitors
Institution:1. Department of Medicinal Chemistry, School of Pharmacy, Qingdao University, Qingdao, Shandong, China;2. Department of Pharmacology, School of Pharmacy, Qingdao University, Qingdao, Shandong, China;3. Department of Pharmacology, College of Basic Medicine, Qingdao University, Qingdao, Shandong, China;1. Department of Pharmacology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, USA;2. Hoxworth Blood Center, University of Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA;3. Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA, USA;1. Faculty of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan;2. Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan;3. Osaka University of Pharmaceutical Science, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan;1. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036, Arcavacata di Rende, CS, Italy;2. CNR-NANOTEC, Licryl-UOS Cosenza and CEMIF. Cal, Dep. of Physics, University of Calabria, Via P. Bucci, 87036, Rende, CS, Italy;3. Centre d’Etudes et de Recherche sur le Médicament de Normandie, Normandie Univ, UNICAEN, CERMN, 14000, Caen, France;4. Chemistry Department, Faculty of Science, Assiut University, 71516, Assiut, Egypt;5. Department of Science, University of Basilicata, Potenza, Italy;1. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China;2. Department of Pharmacology, Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, United States;1. Yncréa Hauts-de-France, Hautes Etudes d’Ingénieur (HEI), UCLille, Health & Environment Department, Team Sustainable Chemistry, Laboratoire de Chimie Durable et Santé, 13 rue de Toul, F-59046 Lille, France;2. Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167 - RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, F-59000 Lille, France;3. ‘Alexandru Ioan Cuza’ University of Iasi, Faculty of Chemistry, Bd. Carol I nr. 11, 700506 Iasi, Romania;4. Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020 – UMR1277 - Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000 Lille, France;5. Plateau de Cytométrie, BioImaging Center Lille Nord de France, BICeL Campus Hospitalo-Universitaire, Lille, France;6. Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Centre de Recherche de Gif, Avenue de la Terrasse, F-91198 Gif-sur-Yvette Cedex, France;7. Université de Lille, Faculté des Sciences Pharmaceutiques et Biologiques, Rue du Pr Laguesse, B.P. 83, F-59006 Lille, France;1. Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China;2. State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), School of Chemistry and Pharmaceutical Sciences of Guangxi Normal University, Guilin 541004, China
Abstract:Histone deacetylases (HDACs) have proven to be promising targets for the development of anti-cancer drugs. In this study, we reported a series of novel chalcone based tubulin and HDAC dual-targeting inhibitors. Three compounds inhibited the activities of HDAC and tubulin polymerization simultaneously and displayed anti-proliferative activities toward eleven human tumor cell lines. Compound 8a remarkably induced growth inhibition, apoptosis and G2/M phase arrest of A549 tumor cells. Finally, the inhibitory activities of 8a against HDAC6 and tubulin were rationalized by molecular docking studies.
Keywords:Histone deacetylase  Tubulin polymerization  Dual-targeting  Chalcone  Inhibitor  Antitumor
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