New Analogues of Amonafide and Elinafide, Containing Aromatic Heterocycles: Synthesis, Antitumor Activity, Molecular Modeling, and DNA Binding Properties
| Autor: | Miguel F. Braña, Cristina Abradelo, Mercedes Yuste, Mónica Cacho, Mónica Báñez-Coronel, Maria Fernanda Rey-Stolle, Ana Ramos, Jose M. Pozuelo, Mario A. García, Juan Carlos Lacal, M. Teresa Domínguez, Beatriz de Pascual-Teresa |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Molecular model Stereochemistry Transplantation Heterologous Organophosphonates Mice Nude Thiophenes Imides Chemical synthesis Mice Structure-Activity Relationship chemistry.chemical_compound Cell Line Tumor Furan Drug Discovery Thiophene Animals Humans Structure–activity relationship Moiety Furans Adenine Amonafide DNA Isoquinolines Amides Intercalating Agents Transplantation Naphthalimides chemistry Molecular Medicine Drug Screening Assays Antitumor Neoplasm Transplantation |
| Zdroj: | Journal of Medicinal Chemistry. 47:1391-1399 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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