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

Abstract

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.

Synthesis, spectral, structural characterization and biological activity of new palladium(II) complexes containing 3‐acetyl‐8‐methoxy‐2H‐chromen‐2‐one derived Schiff bases

“…The absorption results indicated that the new palladium(II) complexes effectively bind to DNA. Further, this has been confirmed by ethidium bromide displacement experiments as done with the reported procedure . The fluorescence quenching spectra of EB bound DNA by the complexes are given in Figure .…”

“…The angles Cl(1)−Pd(1)−S(1) 91.7 (4)° for 2 and 89.0 (9)° for 4 and the angle Cl(1)−Pd(1)−O(1) 89.1 (1)° for 2 and Cl(1)−Pd(1)−O(2) 91.0 (5)° for 4 deviated from the ideal angle 90°. The bite angles observed in the molecular structures of 2 and 4 compare favorably with those of analogous palladium thiosemicarbazone complexes . The trans angles of O(1)−Pd(1)−S(1), 179.0 (1)° for 2 , O(2)−Pd(1)−S(1), 179.0 (2)° for 4 and N(1)−Pd(1)−Cl(1), 177.7 (1)° for 2 and 174.9 (2)° for 4 , indicated a significant deviation from the expected linear trans geometry, suggesting distortion in the square‐planar coordination geometry.…”

“…The variation in the antimicrobial activity of different metal complexes against different pathogens depends on their impermeability of the cell or the differences in ribosomes in microbial cell. The antimicrobial activity of the new palladium(II) complexes were significant when compared with the already reported some palladium(II) complexes …”

Anticancer Properties of Ru and Os Half‐Sandwich Complexes of N,S Bidentate Schiff Base Ligands Derived from Phenylthiocarbamide

“…The same trend is reflected by the IC 50 values obtained from in vitro studies where 1 a and 3 a displayed low [a] taken from ref. [23]. Nd = Not determined to moderate cytotoxicity while the highest cytotoxic potential was exhibited by 2 a.…”