Synthesis,cytotoxicity, DNA binding and topoisomerase II inhibition of cassiarin A derivatives |
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| Institution: | 1. Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand;2. Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand;3. Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand;4. Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, Bangkok 10330, Thailand;1. Institute of Medical Mission, Department of Tropical Medicine, 97074 Würzburg, Germany;2. Laboratory of Molecular Physiology, Institute of Experimental Medicine, School of Medicine Luis Razetti, Faculty of Medicine, Universidad Central de Venezuela, Caracas, Venezuela;3. Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany;1. G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences, 1 Akademicheskaya Str., 153045 Ivanovo, Russian Federation;2. United Physico-Chemical Centre, Ivanovo State University of Chemistry and Technology, Sheremetevskiy av. 10, 153012 Ivanovo, Russian Federation;3. Research Institute of Macroheretocyclic Compounds, Ivanovo State University of Chemistry and Technology, Sheremetevskiy av. 7, 153012 Ivanovo, Russian Federation;1. Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan;2. South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan;3. Integrated Center for Sciences, Tarumi Station, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan;1. Faculté de Pharmacie, Laboratoire de Pharmacologie Marine, 5000 Monastir, Tunisia;2. Torrey Pines Institute for Molecular Studies, Port Saint Lucie, FL 34987, United States;3. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK;1. 2502 Marble NE, MSC09 5360, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA;2. Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131, USA;3. Department of Dermatology, University of New Mexico, Albuquerque, NM 87131, USA;1. Chittaranjan National Cancer Institute, Department of Cancer Chemoprevention, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India;2. Chittaranjan National Cancer Institute, Department of Translational Research, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal, India |
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| Abstract: | Four series of cassiarin A derivatives with alkanoyl (3a–3d), aroyl (4a–4d), hydroxy/amino-substituted ethylene glycol (5a–5c) and selenium-containing (6a) side chains were synthesized. Their antitumor activities were evaluated against BT474, CHAGO, HepG2, KATO-III, SW620 and CaSki cancer cell lines. Preliminary results demonstrated that 5b had moderate activities against HepG2 and KATO-III cell lines, while 5c showed moderate to high cytotoxicity against most tested cell lines. In addition, 6a exhibited moderate cytotoxicity against cervical cells, CaSki. DNA-binding and ethidium bromide displacement experiments suggested that 5c and 5b binds to DNA via an intercalative mode, whereas 6a did not. However, the selenium-containing cassiarin A derivative 6a inhibited topoisomerase II with more than 95% inhibition at the concentration of 50 μM. These cassiarin A derivatives showed lower toxicity to normal cells, WI-38 than amonafide therefore they are potential lead compounds to be further developed as new anticancer agents. |
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| Keywords: | Cassiaria A Amonafide Selenium compound DNA-binding Topoisomerase II |
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