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.
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
Miguel F
MF
Braña
Mónica
M
Cacho
Mario A
MA
García
Beatriz
B
de Pascual-Teresa
Ana
A
Ramos
M Teresa
MT
Domínguez
José M
JM
Pozuelo
Cristina
C
Abradelo
María Fernanda
MF
Rey-Stolle
Mercedes
M
Yuste
Mónica
M
Báñez-Coronel
Juan Carlos
JC
Lacal
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