New analogues of amonafide and elinafide, containing aromatic heterocycles: synthesis, antitumor activity, molecular modeling, and DNA binding properties.
Amonafide- and elinafide-related mono and bisintercalators, modified by the introduction of a pi-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.
Braña
Miguel F
MF
Departamentos de Ciencias Químicas, Facultad de Ciencias Experimentales y de la Salud, Universidad San Pablo CEU, Urbanización Montepríncipe, 28668-Boadilla del Monte, Madrid, Spain. mfbrana@ceu.es
Cacho
Mónica
M
García
Mario A
MA
de Pascual-Teresa
Beatriz
B
Ramos
Ana
A
Domínguez
M Teresa
MT
Pozuelo
José M
JM
Abradelo
Cristina
C
Rey-Stolle
María Fernanda
MF
Yuste
Mercedes
M
Báñez-Coronel
Mónica
M
Lacal
Juan Carlos
JC
D000225:Adenine; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D053644:Naphthalimides; D009368:Neoplasm Transplantation; D063065:Organophosphonates; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014183:Transplantation, Heterologous
D000577:Amides; D005663:Furans; D007094:Imides; D007364:Intercalating Agents; D007546:Isoquinolines; D053644:Naphthalimides; D063065:Organophosphonates; D013876:Thiophenes; C037020:amonafide; D004247:DNA; C092297:elinafide; D000225:Adenine