2. Academic Validation
  3. 5-Ethynylarylnaphthalimides as antitumor agents: Synthesis and biological evaluation

5-Ethynylarylnaphthalimides as antitumor agents: Synthesis and biological evaluation

  • Bioorg Med Chem. 2017 Mar 15;25(6):1976-1983. doi: 10.1016/j.bmc.2017.02.024.
Patricia Quintana-Espinoza 1,  Pedro Martín-Acosta 1,  Ángel Amesty 1,  Patricia Martín-Rodríguez 2,  Isabel Lorenzo-Castrillejo 3,  Leandro Fernández-Pérez 2,  Félix Machín 4,  Ana Estévez-Braun 5
Affiliations

Affiliations

  • 1 Instituto Universitario de Bio-Orgánica Antonio González (CIBICAN), Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain.
  • 2 Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Departamento de Ciencias Clínicas, BIOPHARM, Universidad de Las Palmas de Gran Canaria, Spain.
  • 3 Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario 145, 38010 Santa Cruz de Tenerife, Spain.
  • 4 Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Carretera del Rosario 145, 38010 Santa Cruz de Tenerife, Spain. Electronic address: fmacconw@gmail.com.
  • 5 Instituto Universitario de Bio-Orgánica Antonio González (CIBICAN), Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206 La Laguna, Tenerife, Spain. Electronic address: aestebra@ull.es.
PMID: 28233678 DOI: 10.1016/j.bmc.2017.02.024
Abstract

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.

Keywords

Antiproliferative activity; DNA damage; Naphthalimides; Saccaromyces cereviciae; Topoisomerase II.

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