Linker-modified triamine-linked acridine dimers: Synthesis and cytotoxicity properties in vitro and in vivo

The preparation and cytotoxicity properties of a series of Nε-substituted triamine-linked acridine dimers are described. Most acridine dimer derivatives reveal highly potent in vitro cytotoxicity properties and DNA binding activity. Several acridine dimers were selected to study their action in vivo. These acridine dimers have demonstrated a narrow safe margin, as has adriamycin, but higher maximum tolerate dose (MTD) in comparison with that of adriamycin in ICR mice. The acridine dimers also demonstrated various anit-COLO 205 solid tumor activities in vivo. Compound 1 has shown the most potent solid tumor inhibition.

A series of Nε-substituted 6 or 7 carbons of triamine-linked acridine dimers were synthesized and their biological activity was determined. Most acridine dimer derivatives reveal highly potent cancer cell killing activity with COLO205, HAT22T, SK-BR-3 and MOLT-4 human cancer cell lines by in vitro cytotoxicity assays and DNA binding activity. Some acridine dimers also demonstrated various anit-COLO 205 solid tumor activities in vivo. Compound 1 has shown the most potent solid tumor inhibition.Figure optionsDownload as PowerPoint slide