Isoquino[4,5-bc]acridines: Design, synthesis and evaluation of DNA binding, anti-tumor and DNA photo-damaging ability

Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 μM and cleaved DNA from form I to 100% form II by 50 μM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.