DNA interaction of a fluorescent, cytotoxic pyridinimino platinum(II) complex

Abstract

New pyridinimino complexes of platinum(II) [PtCl₂(N^N-R)] (N^N = 2-pyridylmethanimino, R = -(CH₂)₂O(CH₂)₂OH, -(CH)₂O(CH₂)₂OCH₂Pyr), Pyr = pyren-1-yl) have been prepared. They are characterized by a dioxygenated alkyl side chain and, in one case, by a fluorescent terminal 1-pyrenyl residue. The complexes were characterized by elemental analysis, IR, ¹H-, ¹³C-and ¹⁹⁵Pt NMR spectroscopies. For [PtCl₂(N^N-(CH₂)₂O(CH₂)₂OH] the molecular structure was determined by single crystal X-ray diffraction. The complexes are soluble and stable in DMSO/H₂O (80/20, v/v). The pyrenyl terminated compound was tested as antiproliferative agent against selected human cancer cell lines. Comparable cytotoxic effect was obtained on human ovarian carcinoma A-2780 and A-2780cis cells, thus suggesting a certain ability to circumvent cisplatin resistance. The interaction of this complex with DNA was investigated by linear flow dichroism and by spectrophotometric (absorbance and fluorescence) titrations. Both techniques enlightened the presence of a complex mode of interaction with DNA, involving both groove binding and intercalation.

Keywords: Antiproliferative properties; DNA interaction; Groove binding; Intercalation; Pyridinimino platinum(II) complexes.