ChemInform Abstract: 1-[(ω-Aminoalkyl)amino]-4- [N-(ω-aminoalkyl)carbamoyl]-9-oxo-9,10-dihydroacridines as Intercalating Cytotoxic Agents: Synthesis, DNA Binding, and Biological Evaluation.

✍ Scribed by I. ANTONINI; P. POLUCCI; T. C. JENKINS; L. R. KELLAND; E. MENTA; N. PESCALLI; B. STEFANSKA; J. MAZERSKI; S. MARTELLI

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 33 KB
• Volume: 29
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199808123

✦ Synopsis

1-[(ω-Aminoalkyl)amino]-4-[N-(ω-aminoalkyl)carbamoyl]-9-oxo-9,10dihydroacridines as Intercalating Cytotoxic Agents: Synthesis, DNA Binding, and Biological Evaluation.

-DNA-binding results from thermal denaturation and fluorescence-based studies are reported for the title compounds such as (III), obtained by aminolysis of the corresponding chloro derivatives, with calf thymus DNA and two polyoligonucleotide duplexes. In vitro cytotoxicity data against six tumor cell lines are described. The introduction of a second basic side chain in position 1 of the tricyclic compounds results in an excellent increase in cytotoxicity. The compound (IIIa) is about 40 times more cytotoxic against the L1210 cell line than the corresponding unsubstituted derivative. All 10 examples of the title compounds show a usefully wide spectrum of cytotoxic activity towards a variety of tumor cell lines, although no compound approaches the potency of mitoxantrone. -(ANTONINI, I.;