5-Ethynylarylnaphthalimides as Antitumor Agents: Synthesis and Biological Evaluation

Publication date: Available online 13 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Patricia Quintana-Espinoza, Pedro Martín-Acosta, Ángel Amesty, Patricia Martín-Rodríguez, Isabel Lorenzo-Castrillejo, Leandro Fernández-Pérez, Félix Machín, Ana Estévez-Braun
A set of 5-ethynylarylnaphthalimides was synthesized by Sonogashira cross-coupling reactions and evaluated for antiproliferative and antitopoisomerase II in vitro activities. Furthermore docking studies of these molecules as DNA-intercalators were carried out and the in vivo DNA-damaging activity was also determined with the model organism Saccharomyces cerevisiae. From the obtained results three naphthalimides 6, 13 and 14 showed strong topoisomerase II inhibitory activity. These three molecules also presented good docking scores as DNA-intercalators using a self-complementary oligodeoxynucleotide d(ATGCAT)2 as a model, and compounds 13 and 14 were among the most cytotoxic in the in vivo DNA-damaging activity.

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