Synthesis,characterization, cytotoxicity and computational studies of new phosphine‐ and carbodithioate‐based palladium(II) complexes

In quest of new metallo‐pharmaceuticals with enhanced anticancer activity, four new phosphine‐ and carbodithioate‐based Pd(II) complexes of the type (R)CS₂Pd(PR₃)Cl] (where R = 4‐(2‐hydroxyethyl)piperazine ( 1 , 2 ), dibenzyl ( 3 , 4 ); PR₃ = diphenyl(p ‐tolyl)phosphine ( 1 , 3 ), tris(4‐tolyl)phosphine ( 2 , 4 )) were synthesized and characterized using elemental analysis, Fourier transform infrared and NMR (¹H, ¹³C and ³¹P) spectroscopies and single‐crystal X‐ray diffraction. The X‐ray diffraction data confirmed the pseudo square‐planar geometry ensuring bidentate coordination mode of carbodithioate ligands. Anticancer activity of the synthesized complexes and their ligands was assessed against human lung (A549), breast (MCF‐7) and prostate (PC3) carcinoma cells using MTT assay. All the tested compounds showed activity in micromolar range. In many cases, the cytotoxicity of the synthesized complexes was higher than or comparable to that of the standard drugs cisplatin and doxorubicin. Complex 3 emerged as the most promising compound with the lowest IC₅₀ values of 4.83, 3.72 and 5.11 μM for A549, MCF‐7 and PC3 carcinoma cell lines, respectively. DNA binding studies were also carried out using UV–visible spectroscopy. We extended our investigations to explore the mechanism of anticancer activity using in silico tools. Based on the mechanism of action of standard drugs used, extensive docking studies were carried out on the three different biomolecular targets.