Ni(II), Pd(II), and Pt(II) Complexes of the Hedgehog Pathway Inhibitor GANT61-D

GANT61-D is an important hedgehog pathway inhibitor and an interesting ligand candidate for metal coordination. The first examples of metal complexes of the potent hedgehog pathway inhibitor GANT61-D are described. The reaction of Ni(II), Pd(II), and Pt(II) precursors with the hedgehog pathway inhibitor GANT61-D gave [Ni^II(GANT61-D)(OH₂)₃(μ²-SO₄)(μ³-SO₄)] (1), [Pd^II(Cl)(GANT61-D)]Cl (2), [Pt^II(Cl)(GANT61-D)]Cl, and [Pt^II(CBDCA_-2H)(GANT61-D)]. X-ray crystal structure analysis revealed that GANT61-D is a versatile N-donor ligand that can act as a bidentate ligand via the diaminopropane (DAP) N atoms or a tridentate ligand via the DAP N atoms and one dimethylaniline N atom. Protonation constants of the GANT61-D ligand in water and in a 60:40 (w/w) dimethyl sulfoxide-water solvent mixture were determined. Potentiometric and spectroscopic data on the Ni^II(GANT61-D) system indicate the formation of octahedral 1:1 species with medium stability in solution. 1 and 2 exhibited noteworthy in vitro cytotoxicity against medulloblastoma cancer cells.