Pd(II) complexes with N-substituted pyrazoles as ligands. The influence of the R group [OMe versus NMe2] of [1-{R–(CH2)2–}-3,5-Ph2–(C3HN2)] on their cytotoxic activity on breast cancer cell lines

•Mono and di Pd(II) complexes with N-{(CH2)2–R}-3,5-diphenylpyrazole (R = OMe) as ligands.•The influence of the R groups (OMe versus NMe2) on the reactivity, properties and activities.•Pd(II) complexes are more potent than the free pyrazolyl ligand in MCF7 and MDA-MB231 breast cell lines.•Palladacycles with cytotoxic activity similar to cisplatin in the triple negative MDA-MB231 breast cancer cell lines.

The study of the reactivity of the novel pyrazole derivative [1-{MeO–(CH2)2–}-3,5-Ph2–(C3HN2)] (1) with Na2[PdCl4] or Pd(OAc)2 under different experimental conditions has allowed us to isolate and characterize the trans-isomers of [Pd{[1-{MeO–(CH2)2–}-3,5-Ph2–(C3HN2)]}2(X)2] [X = Cl (2) or OAc (3)] and the di-μ-ligand bridged cyclopalladated complexes [Pd{κ2,C,N[1-{MeO–(CH2)2–}-3-(C6H4),5-Ph-(C3HN2)]}(μ-X)]2 [X = OAc (4) or Cl (5)]. Further treatment of compounds 4 or 5 with PPh3 in CH2Cl2 produced the bridge splitting and the formation of [Pd{κ2,C,N[1-{MeO–(CH2)2–}-3-(C6H4),5-Ph-(C3HN2)]}X(PPh3)] [X = OAc (6) or Cl (7)]. The cytotoxic assessment of the free ligand (1) and the Pd(II) complexes on the two breast cancer cell lines MCF7 and MDA-MB231 reveals that: a) compound 1 is less active than its analogue [1-{Me2N–(CH2)2–}-3,5-Ph2–(C3HN2)] (Ic) and b) palladacycles 4–7 showed a remarkable cytotoxic activity in the MDA-MB231 cell line (with IC50 values in the range 9.1–14.4 μM).

Graphical abstractPd(II) complexes with the pyrazole: [1(MeO –CH2CH2)-3,5Ph2–(C3HN2)] acting as N-or [C(phenyl), N(pyrazole)]− ligand are reported. Their antiproliferative activity in MCF7 and MDA-MB231 breast cell lines revealed that some of the palladacycles had cytotoxic activity similar to that of cisplatin in the MDA-MB231 cell line.Figure optionsDownload full-size imageDownload as PowerPoint slide