This work compares the biological properties of cis-diammine- dichloroplatinum (cisplatin) and its new analogue cis-[Pt(AF)2Cl2] (AF stands for 3-aminoflavone), which contains two aminoflavone substituents as non-leaving ligands. Both compounds were tested for their antiproliferative activity against cultured L1210 cells, and their DNA interstrand crosslinking activity in cells and in a cell-free system. Cisplatin was found to be an approximately 6 times more cytotoxic drug than its new analogue. Platinum complexes reacted with purified calf thymus DNA in a cell-free system producing DNA interstrand crosslinks. The kinetics of crosslink formation was very similar for both compounds but the maximal level of crosslinks was 20% higher for cisplatin. In cells, however, crosslinks were produced by cisplatin, whereas this type of DNA lesion was almost undetected in cells treated with the aminoflavone analogue as assayed by DNA alkaline elution. At higher drug concentrations, strong degradation of DNA was observed in L1210 cells treated with cis- [Pt(AF)2Cl2] but not in the cells incubated with cisplatin. This DNA degradation seems to reflect very efficient apoptosis induction by cis-[Pt(AF)2Cl2] as the electrophoretic patterns of DNA from cells incubated with this drug showed a ladder typical for apoptotic cells.
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