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Design,synthesis and biological evaluation of lapachol derivatives possessing indole scaffolds as topoisomerase I inhibitors
Institution:1. School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China;2. Basic Medicine College, Xinxiang Medical University, Xinxiang 453003, China;1. Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece;2. Department of Chemical Engineering, University of Patras, P.O. Box 1407, 26504, Greece;3. FORTH/ICE-HT, P.O. Box 1414, GR-26504 Patras, Greece;1. Institute of Physiologically Active Compounds Russian Academy of Sciences, Chernogolovka 142432, Russia;2. Emanuel Institute of Biochemical Physics Russian Academy of Sciences, Moscow 119334, Russia;3. Institute of Organic Synthesis of the Russian Academy of Sciences, S. Kovalevskaya Str., 22, Ekaterinburg 620041, Russia;4. Ural Federal University, Mira St. 19, Ekaterinburg 620002, Russia;5. Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA;6. Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA;1. Department of Science Education, Jeonju University, Jeonju 560-759, Republic of Korea;2. Department of Carbon Fusion Engineering, Jeonju University, Jeonju 560-759, Republic of Korea;1. Departamento de Química, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil;2. Departamento de Química, ICEB, Universidade Federal de Ouro Preto, CEP 35400-000 Ouro Preto, MG, Brazil;3. Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, CEP 13560-970 São Carlos, SP, Brazil;4. Departamento de Gerontologia, Universidade Federal de São Carlos, CP 676, CEP 13565-905 São Carlos, SP, Brazil;1. Department of Biotechnology, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502285, India;2. Department of Chemistry, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502285, India;3. Department of Chemistry, Indian Institute of Technology Patna, Bihar, Patna 801106, India;4. Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Kandi, Sangareddy 502285, India;1. Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Faculty of Pharmacy, Medical University, Muszyńskiego 1, 90-151 Lodz, Poland;2. Central Scientific Laboratory, Medical University, Mazowiecka 6/8, 92-215 Lodz, Poland;3. Laboratory of Radiopharmacy, Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Faculty of Pharmacy, Medical University, Muszyñskiego 1, 90-151 Lodz, Poland
Abstract:A series of novel lapachol derivatives possessing indole scaffolds was designed and synthesized. The in vitro anti-proliferative activity of these novel compounds was evaluated in Eca109 and Hela cell lines. Almost all the tested compounds showed manifested potent inhibitory activity against the two tested cancer cell lines. Topo I-mediated DNA relaxation activity indicated that these novel compounds have potent Topoisomerase I inhibition activity. The most potent compounds 4n and 4k demonstrated more cytotoxicity than camptothecin and was comparable to camptothecin in inhibitory activities on Topoisomerase I in our biological assay. In addition, the Hoechst 33342 staining method also showed that the complex can induce Hela cell apoptosis.
Keywords:Lapachol  Indole  Molecular hybridization  Anti-proliferative  Topoisomerase I
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