5‐Nitrofuryl‐Containing Thiosemicarbazone Gold(I) Compounds: Synthesis, Stability Studies, and Anticancer Activity

Abstract

This work describes the synthesis of four gold(I) [AuClL] compounds containing chloro and biologically active protonated thiosemicarbazones based on 5‐nitrofuryl (L=HSTC). The stability of the compounds in dichloromethane, DMSO, and DMSO/culture media solutions was investigated by spectroscopy, cyclic voltammetry, and conductimetry, indicating the formation overtime of cationic monometallic [Au(HTSC)(DMSO)]± or [Au(HTSC)2]±, and/or dimeric species. Neutral [{Au(TSC)}2] species were obtained from one of the compounds in dichlomethane/n‐hexane solution and characterized by X‐ray crystallography revealing a Au−Au bond, and deprotonated thiosemicarbazone (TSC). The cytotoxicity of the gold compounds and thiosemicarbazone ligands was evaluated against selected cancer cell lines and compared to that of Auranofin. Studies of the most stable, cytotoxic, and selective compound on a renal cancer cell line (Caki‐1) demonstrated its relevant antimigratory and anti‐angiogenic properties, and preferential accumulation in the cell nuclei. Its mode of action seems to involve interaction with DNA, and subsequent cell death via apoptosis.

Mechanism of Anti-Trypanosoma cruzi Action of Gold(I) Compounds: A Theoretical and Experimental Approach

“…These studies showed that the compounds evolve in solution to cationic monometallic species ([Au(HL)(DMSO)] + or [Au(HL)] + ) and/or to neutral dimeric compounds, [{Au(HL)} 2 ], which always contain the thiosemicarbazone ligands. Compound 2 was the most stable in DMSO and DMSO/culture medium solution for over a week or 72 h, respectively, and was the most cytotoxic and selective compound against different cancer cell lines [18]. In the present work, 2 and 3 were the most active compounds, and particularly compound 2 was also the most selective against T. cruzi.…”

“…As previously mentioned, the [AuCl(HL)] (1-4) compounds had been recently synthesized and fully characterized in solid state and solution [18]. However, no crystallographic data of the monomeric structures had been obtained due to the low solution stability reported for these complexes.…”

“…Recently, gold(I) compounds that include 5-nitrofuryl-containing thiosemicarbazones were synthesized and fully characterized [18]. The [AuCl(HL)] complexes (Figure 1) were evaluated as potential anticancer agents in a panel of human cancer cells.…”

“…The [AuCl(HL)] complexes (Figure 1) were evaluated as potential anticancer agents in a panel of human cancer cells. The complexes demonstrated high activity and selectivity, and their main mechanism of action was related to the capacity of the compounds to accumulate in the cancer cell nuclei and interact with DNA, which caused subsequent cancer cell death via apoptosis [18].…”

“…It has been previously determined that the [AuCl(HL)] compounds present partition coefficient (log P) values between −0.31 to 0.26 [18]. In this work, the lipophilicity was experimentally determined using reversed-phase TLC.…”