Large-bite bis(phosphite) ligand containing mesocyclic thioether moieties: synthesis, reactivity, group 11 (Cu~I, Au~I) metal complexes and anticancer activity studies on a human cervical cancer (HeLa) cell line

摘要

The large-bite bis(phosphite) ligand [{(-OC_(10)H6(μ-S)C_(10)H6O-)P{μ-(-OC_(10)H6(μ-S)C_(10)H6O-)}-P(-OC_(10)H6(μ-S)C_(10)H6O-)}] (P^P) (2) was obtained by the reaction of PCl3 and thiobis(2,2'-naphthol) (1). The stoichiometric reactions of 2 with elemental sulfur and selenium afforded the corresponding chalcogenide derivatives [(E)P^P(E)] (3, E = S; 4, E = Se) in good yield. Treatment of two equivalents of [ClAu(SMe2)] with 2 afforded a dinuclear complex [ClAu(P^P)AuCl] (5), whereas the 1 :1 reaction with Cul yielded the [(P^P)CuI] (6) complex. The copper(I) complex 6 on treatment with various pyridyl derivatives, produced mixed-ligand complexes [(P^P)CuI(NC5H5)] (7), [(P^P)Cu(2,2'-bpy)]I (8), [(P^P)Cu(1,10-phen)]I (9) and {[(P^P)Cu(4,4'-bpy)]I}_∞ (10). The compounds 2-5 were tested for their cytotoxic activity on the human cervical cancer (HeLa) cell line. Compounds 2 and 3 were found to inhibit proliferation of HeLa cells significantly. These agents also induced apoptotic cell death in cancer cells. Evidence presented in this study indicated that the compounds 2 and 3 activate the tumor suppressor protein p53 in the colon adenocarcinoma (HCT-116) cell line.