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

The stability of new gold(I) containing chloro and biologically active thiosemicarbazones in coordinating and non-coordinating solvents is presented, allowing for a description of potential species formed. The most stable compound (2) results cytotoxic, apoptotic, antimetastatic, and antiangiogenic in a renal cancer cell line like Auranofin but with higher selectivity. 2 accumulates in the nuclei and shows interaction with CT DNA.

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.

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