Cyclopalladated benzophenone imines: Synthesis, cytotoxicity against human breast adenocarcinoma cell lines and DNA interaction

Abstract Treatment of benzophenone imine with the stoichiometric amount of Pd(OAc) 2 in acetic acid at 60 °C produced the corresponding acetato-bridged five-membered ortho -cyclopalladated dimer [Pd{C 6 H 4 CPh NH}(μ-OAc)] 2 ( 1 ), which was isolated in pure form in a 79% yield. Reaction of 1 with an excess of LiCl in acetone gave rise to the corresponding chlorido-bridged cyclopalladated dimer [Pd{C 6 H 4 CPh NH}(μ-Cl)] 2 ( 2 ) in a 78% yield. Compounds 1 – 2 reacted with an excess of py- d 5 or the stoichiometric amount of PPh 3 to give the mononuclear compounds trans - N , L -[Pd{C 6 H 4 CPh NH}(X)(L)] [ 3 (X = OAc, L = py- d 5 ); 4 (X = Cl, L = py- d 5 ); 5 (X = OAc, L = PPh 3 ) and 6 (X = Cl, L = PPh 3 )]. Compounds 2 – 3 were prepared in CDCl 3 /py- d 5 solution and were studied by 1 H NMR, but were not isolated. In contrast, compounds 5 – 6 were prepared in acetone and were isolated in pure form in 43 and 79% yields, respectively. Compounds 1 , 2 , 5 and 6 were characterized by elemental analyses, mass spectrometry, IR, NMR and electronic spectroscopy. Compounds 1 , 2 , 5 and 6 showed high antiproliferative activity against MDA-MB231 and MCF7 human breast cancer cell lines, especially, compounds 5 – 6 . These two latter compounds presented greater antiproliferative activity than cisplatin and produced IC 50 values in the range 1–5 μM. The interaction of compounds 1 , 2 , 5 and 6 with DNA was also studied by the DNA electrophoretic migration, DNA-ethidium bromide fluorescence quenching and viscometry techniques.