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

New pyridinimino complexes of platinum(II) [PtCl 2 (N^N-R)] (N^N = 2-pyridylmethanimino, R = -(CH 2) 2 O(CH 2) 2 OH, -(CH) 2 O(CH 2) 2 OCH 2 Pyr), 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 [PtCl 2 (N^N-(CH 2) 2 O(CH 2) 2 OH] the molecular structure was determined by single crystal X-ray diffraction. The complexes are soluble and stable in DMSO/H 2 O (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. DNA interaction of a fluorescent, cytotoxic pyridinimino platinum(II) complex. Riccardo Bondi, Tarita Biver, Lisa Dalla Via, Federica Guarra, Mariafrancesca Hyeraci, Claudia Sissi, Luca Labella, Fabio Marchetti and Simona Samaritani. A versatile pyridinimino Pt(II) complex, bearing a pyrenyl-terminated side chain was synthesized. The complex circumvents cisplatin resistance towards A2780cis cells and is able to interact with DNA by both groove binding and intercalation. Unlabelled Image • A fluorescently tagged, cytotoxic pyridinimino platinum(II) complex was prepared. • The complex circumvents cisplatin resistance against A2780cis cancer cell line. • Complex/DNA interaction was studied by independent spectroscopic techniques. • DNA interaction takes place by both groove binding and intercalation. [ABSTRACT FROM AUTHOR]