Portal de Periódicos da CAPES

New Analogues of Amonafide and Elinafide, Containing Aromatic Heterocycles: Synthesis, Antitumor Activity, Molecular Modeling, and DNA Binding Properties

2004; American Chemical Society; Volume: 47; Issue: 6 Linguagem: Inglês

10.1021/jm0308850

1520-4804

Miguel F. Braña, Mónica Cacho, Mario A. García, Beatriz de Pascual‐Teresa, Ana Ramos, M. Teresa Domínguez, José Manuel Pozuelo, Cristina Abradelo, Fernanda Rey-Stolle, M. Yuste, Mónica Báñez-Coronel, Juan Carlos Lacal,

Cancer therapeutics and mechanisms

Amonafide- and elinafide-related mono and bisintercalators, modified by the introduction of a π-excedent furan or thiophene ring fused to the naphthalimide moiety, have been synthesized. These compounds have shown an interesting antitumor profile. The best compound, 9, was 2.5-fold more potent than elinafide against human colon carcinoma cells (HT-29). Molecular dynamic simulations and physicochemical experiments have demonstrated that these compounds are capable of forming stable DNA complexes. These results, together with those previously reported by us for imidazo- and pyrazinonaphthalimide analogues, have prompted us to propose that the DNA binding process does not depend on the electronic nature of the fused heterocycle.