1. Academic Validation
  2. Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides

Synthesis and study of antiproliferative, antitopoisomerase II, DNA-intercalating and DNA-damaging activities of arylnaphthalimides

  • Bioorg Med Chem. 2013 Nov 1;21(21):6484-95. doi: 10.1016/j.bmc.2013.08.039.
Patricia Quintana-Espinoza 1 Jonay García-Luis Angel Amesty Patricia Martín-Rodríguez Isabel Lorenzo-Castrillejo Angel G Ravelo Leandro Fernández-Pérez Félix Machín Ana Estévez-Braun
Affiliations

Affiliation

  • 1 Instituto Universitario de Bio-Orgánica 'Antonio González', Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain; Instituto Canario de Investigación del Cáncer (ICIC), Spain(†).
Abstract

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.

Keywords

Antiproliferative activity; Arylnaphthalimides; DNA damage; Saccharomyces cerevisiae; Topoisomerase II.

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