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Título: | Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides |
Autor: | Martín-Rodríguez, Patricia CSIC; Fernández-Pérez, Leandro CSIC ORCID; Estévez-Braun, Ana | Palabras clave: | Topoisomerase II Antiproliferative activity Saccharomyces cerevisiae DNA damage Arylnaphthalimides |
Fecha de publicación: | 2013 | Editor: | Elsevier | Citación: | Bioorganic and Medicinal Chemistry 21(21): 6484-6495 (2013) | Resumen: | A series of arylnaphthalimides were designed and synthesized to overcome the dose-limiting cytotoxicity of N-acetylated metabolites arising from amonafide, the prototypical antitumour naphthalimide whose biomedical properties have been related to its ability to intercalate the DNA and poison the enzyme Topoisomerase II. Thus, these arylnaphthalimides were first evaluated for their antiproliferative activity against two tumour cell lines and for their antitopoisomerase II in vitro activities, together with their ability to intercalate the DNA in vitro and also through docking modelization. Then, the well-known DNA damage response in Saccharomyces cerevisiae was employed to critically evaluate whether these novel compounds can damage the DNA in vivo. By performing all these assays we conclude that the 5-arylsubstituted naphthalimides not only keep but also improve amonafide's biological activities. | Descripción: | et al. | URI: | http://hdl.handle.net/10261/124134 | DOI: | 10.1016/j.bmc.2013.08.039 | Identificadores: | doi: 10.1016/j.bmc.2013.08.039 issn: 0968-0896 e-issn: 1464-3391 |
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