Synthesis, anti-proliferative and apoptosis-inducing studies of palladacycles containing a diphosphine and a Sn,As-based chelate ligand

Abstract

Cleavage of the bromide bridges in [Pd₂(μ-Br)₂{κ²(Sn,As)-2-MeBrSnC₆F₄AsPh₂}₂] (1) by diphosphine ligands gave the mono- and dinuclear palladacycles [Pd(L)Br{κ²(Sn,As)-2-MeBrSnC₆F₄AsPh₂}] [L = dppe (2) dppm (3), ortho-dppBz (4)] and [Pd₂Br₂(para-dppBz){κ²(Sn,As)-2-MeBrSnC₆F₄AsPh₂}₂] (5). The interactions of these complexes with DNA (CT-DNA) and proteins (human serum albumin) were studied by UV-Vis and fluorescence spectroscopy, respectively. The results confirmed the interaction of these palladium complexes with CT-DNA through groove binding, and their strong binding affinity to HSA. The anti-proliferative activities of complexes 1–5 were tested against four human cancer cell lines (HeLa, A549, PC-3, and HT1080) and normal keratinocytes (HaCaT). Among the series, the palladium(II) complex containing the 1,2-bis(diphenylphosphino)benzene ligand (4) showed the highest cytotoxicity against HeLa, PC-3 and HT1080 cells, with IC₅₀ values of 0.25 ± 0.08, 0.85 ± 0.11, and 0.66 ± 0.15 μM, respectively. Interestingly, compound 4 exhibited lower cytotoxic activity toward normal HaCaT cells (IC₅₀ = 4.65 ± 0.16 μM). Additionally, this complex exhibited lower toxicity and better anti-cancer activity than cisplatin. Further mechanistic studies, including Hoechst staining and flow cytometry, confirmed that complex 4 induced G2/M phase cell cycle arrest and apoptotic cell death in HeLa cells.