Design,synthesis and in vitro cytotoxicity evaluation of 5-(2-carboxyethenyl)isatin derivatives as anticancer agents |
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| Affiliation: | 1. Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China;2. Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China;3. College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, PR China;4. Chemo Dynamics, Inc., 3 Crossman Road South, Sayreville, NJ 08872, USA;1. Department of Chemistry, National Institute of Technology, Tiruchirappalli 620015, India;2. Department of Physics, Dr. MGR Educational and Research Institute University, Maduravoyal, Chennai 600095, India;3. Department of Biotechnology, Dr. MGR Educational and Research Institute University, Maduravoyal, Chennai 600095, India;4. Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600025, India;1. Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India;2. Lloyd Institute of Management and Technology, Greater Noida, UP, India;3. Indian Institute of Integrative Medicine, Jammu, India;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;3. Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO Box 2476, Melbourne 3001, Australia;1. School of Pharmaceutical Sciences, Rajiv Gandhi Technical University, Airport Bypass Road, Gandhi Nagar, Bhopal 462036, (M.P.), India;2. Tumour Biology Group, Northeast Cancer Centre, Health Sciences North, 41, Ramsey Lake Road, Sudbury, Ontario P3E 5J1, Canada;3. Department of Biology, Laurentian University, Sudbury, Ontario P3E 2C6, Canada;1. College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, China;2. College of Life Sciences, NanKai University, Tianjin 300071, China;3. College of Pharmacy, NanKai University, Tianjin 300071, China;4. High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China |
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| Abstract: | Forty four di- or trisubstituted novel isatin derivatives were designed and synthesized in 5–6 steps in 25–45% overall yields. Their structures were confirmed by 1H NMR and 13C NMR as well as LC–MS. The anticancer activity of these new isatin derivatives against three human tumor cell lines, K562, HepG2 and HT-29, were evaluated by MTT assay in vitro. SAR studies suggested that the combination of 1-benzyl and 5-[trans-2-(methoxycarbonyl)ethen-1-yl] substitution greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 as present in the parent ring is required to such a potency. This study leads to the identification of two highly active molecules, compounds 2h (IC50 = 3 nM) and 2k (IC50 = 6 nM), against human leukemia K562 cells. |
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| Keywords: | Isatin derivatives In vitro cytotoxicity Antitumor activity |
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