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

The large-bite bis(phosphite) ligand [{(–OC₁₀H₆(μ-S)C₁₀H₆O–)P{μ-(–OC₁₀H₆(μ-S)C₁₀H₆O–)}P(–OC₁₀H₆(μ-S)C₁₀H₆O–)}] (PP) (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)PP(E)] (3, E = S; 4, E = Se) in good yield. Treatment of two equivalents of [ClAu(SMe₂)] with 2 afforded a dinuclear complex [ClAu(PP)AuCl] (5), whereas the 1 : 1 reaction with CuI yielded the [(PP)CuI] (6) complex. The copper(I) complex 6 on treatment with various pyridyl derivatives, produced mixed-ligand complexes [(PP)CuI(NC₅H₅)] (7), [(PP)Cu(2,2′-bpy)]I (8), [(PP)Cu(1,10-phen)]I (9) and {[(PP)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.