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

Abstract

The study of the reactivity of the novel pyrazole derivative [1-{MeOe(CH2)2e}-3,5-Ph2e(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-{MeOe(CH2)2e}-3,5-Ph2e(C3HN2)]}2(X)2] [X ¼ Cl (2) or OAc (3)] and the di-m-ligand bridged cyclopalladated complexes [Pd{k2,C,N[1-{MeOe(CH2)2e}-3-(C6H4),5-Ph- (C3HN2)]}(m-X)]2 [X ¼ 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{k2,C,N[1-{MeOe(CH2)2e}-3-(C6H4),5-Ph- (C3HN2)]}X(PPh3)] [X ¼ 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-{Me2Ne(CH2)2e}-3,5-Ph2e(C3HN2)] (Ic) and b) palladacycles 4e7 showed a remarkable cytotoxic activity in the MDA-MB231 cell line (with IC50 values in the range 9.1e14.4 mM).