Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenine
-
Amides / chemical synthesis*
-
Amides / chemistry
-
Amides / pharmacology
-
Animals
-
Cell Line, Tumor
-
DNA / chemistry*
-
Drug Screening Assays, Antitumor
-
Furans / chemical synthesis
-
Furans / chemistry
-
Furans / pharmacology
-
Humans
-
Imides / chemical synthesis*
-
Imides / chemistry
-
Imides / pharmacology
-
Intercalating Agents / chemical synthesis*
-
Intercalating Agents / chemistry
-
Intercalating Agents / pharmacology
-
Isoquinolines / chemical synthesis*
-
Isoquinolines / chemistry
-
Isoquinolines / pharmacology
-
Mice
-
Mice, Nude
-
Models, Molecular
-
Naphthalimides
-
Neoplasm Transplantation
-
Organophosphonates
-
Structure-Activity Relationship
-
Thiophenes / chemical synthesis
-
Thiophenes / chemistry
-
Thiophenes / pharmacology
-
Transplantation, Heterologous
Substances
-
Amides
-
Furans
-
Imides
-
Intercalating Agents
-
Isoquinolines
-
Naphthalimides
-
Organophosphonates
-
Thiophenes
-
amonafide
-
DNA
-
elinafide
-
Adenine