Novel DNA bis-intercalators of isoquinolino[4,5-bc]acridines: design, synthesis and evaluation of cytotoxic activity

Mono- and dinuclear isoquinolino[4,5-bc]acridine derivatives were designed and facilely synthesized, their DNA-binding affinities and cytotoxic activities were evaluated. induced unwinding of supercoiled plasmid pBR 322 DNA by (36±2)° while induced that by (41±1)°, both of which were higher than the mono-analogue ((19±2)°). exhibited the highest in vitro antitumor activity against human lung cancer cell (A549) and was the most active one against murine leukemia cell (P388). DNA binding constant and molecular model indicated that both the length of linker chain and the distance of interchromophore were key impact factors for DNA binding affinity and biological activity.