Silver(I) complexes of methyl xanthate against human adenocarcinoma breast cancer cells

Abstract

The sodium salt of methyl xanthate derives from the reaction of carbon disulfide and sodium hydroxide (1:1) in methanol. Addition of an acetonitrile solution of silver nitrate and tri-aryl-phosphine in 1:2 molar ratio, form the complexes with general formula [Ag(CH3OCS2)(Ar3P)2] (Ar3P=triphenylphosphine (tpp, 1), tri(p-tolyl)phosphine (tptp, 2) and tri(m-tolyl)phosphine (tmtp, 3)). The complexes have been characterized by melting point, FT-IR, UV–Vis, 1H, 31P NMR spectroscopic data and X-ray crystallography. The stability of the Ag–P bond in solution was determined by 31P NMR resonances signals. The photosensitivity of 1–3 against UVB radiation is studied by means of UV–Vis spectroscopy. The stronger photosensitivity is exhibited by 1. The LogP was calculated in order to correlate the influence of lipophilicity on biological activity. The steric demands of arylphosphine were assessed through determination of the cone angles, volumes and H-all atom contacts. Complex of tri(m-tolyl)phosphine exert the greatest steric repulsion (higher cone angle). Hirshfeld surface volumes (2 occupied the greatest space) were analyzed to clarify the nature of the intermolecular interactions. Complexes 1–3 were tested for their in vitro cytotoxic activity against human adenocarcinoma cancer cell lines: MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, estrogen receptor (ER) negative) and MRC-5 (normal human fetal lung fibroblast cells) with sulforhodamine B (SRB) colorimetric assay. Molecule 3 with the lower H-all atoms inter-molecular interactions exhibits the higher activity against MCF-7 cells. The results are correlated with those obtained from heteroleptic silver complexes of tri-aryl-phosphines and carboxylates analogs to 1–3 where the xanthate is replaced by carboxylates. The structure activity relationships (SAR) study underlines the significance of the ligand type on the bioactivity of these compounds.