A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors |
| |
| Institution: | 1. Biomedical Research Centre, Kidscan Laboratories, School of Science, Engineering and Environment, University of Salford, Salford, UK;2. Central Laser Facility, Research Complex at Harwell, Rutherford Appleton Laboratory, STFC, Chilton, Oxfordshire OX11 0QX, UK;1. Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China;2. Central laboratory, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250012, PR China;1. Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Nanjing 211189, China;2. Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China;1. Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia, Egypt;2. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University, Minia, Egypt;3. Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, Egypt;4. Cancer Biology Laboratory, Center of Excellence for Advanced Sciences, National Research Center, Cairo, Egypt;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt;2. Medicinal Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;3. Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University-Kantra Branch, Egypt;4. Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt |
| |
| Abstract: | A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G2/M phase further confirming their ability to inhibit tubulin polymerisation. |
| |
| Keywords: | Combretastatin A-4 Tubulin Cancer Microtubules |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
