Synthesis, structural characterization and in vitro cytotoxicity of new Au(III) and Au(I) complexes with thioamides

Abstract

The reactions of tetrachloroauric(III) acid (HAuCl4) with the thioamides; 2-mercapto-benzothiazole (mbztH) and 5-ethoxy-2-mercapto-benzimidazole (EtmbzimH) lead to the desulfuration of the ligands and the formation of the ionic complexes {[AuCl4]- [bztH2]+} (1), and {[AuCl4]- [EtbzimH2]+ (H2O)} (2) (where bztH2+ and EtbzimH2+ are the desulfurated cations of the starting ligands). The reaction of HAuCl4 with 2-mercapto-nicotinic acid (mnaH2), however results in the formation of 2-sulfonate-nicotininc acid (C6H5NO5S) (3) with the simultaneous oxidation of the sulfur atom. On the other hand, the reactions of the gold(I) complex [Au(tpp)Cl] (4) (tpp = triphenylphosphine (Ph3P)) with the thioamides; 2-mercapto-thiazolidine (mtzdH), 2-mercapto-benzothiazole (mbztH) and 5-chloro-2-mercapto-benzothiazole (ClmbztH) in the presence of potassium hydroxide resulted in the formation of the gold(I) complexes of formulae [Au(tpp)(mtzd)] (5), [Au(tpp)(mbzt)] (6) and [Au(tpp)(Clmbzt)] (7) without ligand desulfuration. All complexes have been characterized by elemental analysis, FT-IR, far-FT-IR,1H-NMR, spectroscopic techniques and X-Ray crystallography. The electrochemical behavior of 1, 2 and 4-7 complexes and the ligands EtmbzimH, mbztH and mnaH2 was also studied in acetonitrile and DMF using cyclic voltammetry. The results are in support of a mechanism of desulfuration of the ligands by Au(III), involving a first oxidation of S to -SO3-, followed by a C-S bond cleavage. This is also supported by PM6 calculations of bond dissociation energies of the various compounds involved. Complexes 1, 2 and 4-7 were tested for in vitro cytotoxicity against leiomyosarcoma cells and the results are discussed in relation with the geometry of the complexes and compared with those of cisplatin and other metals. Complexes 1 and 5 showed higher activity than that of cisplatin, while HAuCl4 was inactive against sarcoma cells.

A spectroscopic and electrochemical investigation of the oxidation pathway of glycyl-d,l-methionine and its N-acetyl derivative induced by gold(III)

“…Au(III) is very short-lived in the presence of different biomolecules because it can rapidly oxidize them, thereby being reduced to Au(I). It has been known for some time that Au(III) can oxidize thiols to disulfides [28,29], cleave the disulfide bond of cystine to give the sulfonic acid [28][29][30][31], oxidize dialkyl sulfides to sulfoxide [32], the sulfur atom of the amino acid methionine stereospecifically to methioninesulfoxide [33][34][35][36][37], and can desulfonate thioamides [38]. The structural consequences of these reactions can play an important role in the toxic side effects of gold-based drugs.…”

Characterization and Antitumor Activity of Chitosan/Poly (Vinyl Alcohol) Blend Doped with Gold and Silver Nanoparticles in Treatment of Prostatic Cancer Model

“…However, the IC 50 value for PC3 cancer cells of complexes showed that the complexe (1) is relatively more effective cytotoxic agent than complexes (2) and (3) which is comparable to cisplatin [52]. Gold complexes have recently gained significant attention as a class of compounds with different pharmacodynamic and kinetic properties than cisplatin with strong cell growth inhibiting effects [53,54]. The cell growth inhibiting effects, in many cases, could be related to anti-mitochondrial effects that make the gold complexes interesting [53,55,56].…”

“…Gold complexes have recently gained significant attention as a class of compounds with different pharmacodynamic and kinetic properties than cisplatin with strong cell growth inhibiting effects [53,54]. The cell growth inhibiting effects, in many cases, could be related to anti-mitochondrial effects that make the gold complexes interesting [53,55,56]. However, the NPs can be incorporated with dual targets, the androgen receptor (AR1) which is a target for prostatic cancer therapy and a G protein receptor (GRC6A), which is seen upregulated in cancer prostate.…”

Inhibition of lipoxygenase (LOX) and anticancer activity caused by gold(I) mixed ligands complexes of triphenylphosphine and thioamides

“…Gold thiolates are used clinically against rheumatoid arthritis 1 . Auronofin (triethylphosphine-gold(I) thioglugose (Et3PAuTg)) and its second generation drug Ridaura TM (triethylphosphine(2,3,4,6-tetra-acetyl-glycopyrasonato-S-)gold(I)), an extensively gold(I) anti-arthritic drug in use, were found to be highly cytostatic to tumour cells and active against i.p.…”