Synthesis, antitumor activity, molecular modeling, and DNA binding properties of a new series of imidazonaphthalimides.
A series of mono and bisintercalators based on the 5,8-dihydrobenz[de]imidazo[4,5-g]isoquinoline-4,6-dione system were synthesized and evaluated for growth inhibitory properties in several human cell lines. All target compounds showed activity in the micromolar range. Representative compounds were evaluated using UV--vis spectroscopy and viscosimetric determinations, showing that they behave as DNA intercalators. Molecular modeling techniques were used in order to rationalize the moderate activity observed for bisnaphthalimides.
Braña
Miguel F
MF
Departamentos de Química Orgánica y Farmacéutica, 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
Acero
Nuria
N
Llinares
Francisco
F
Muñoz-Mingarro
Dolores
D
Abradelo
Cristina
C
Rey-Stolle
María Fernanda
MF
Yuste
Mercedes
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D007364:Intercalating Agents; D009281:Naphthalenes