Cytotoxicity, gold complexes

A considerable amount of the gold that accumulates in the kidneys and liver of mammalian species is bound to MTs. This buildup of gold in the kidneys is accompanied by elevated levels of renal copper to form copper-rich, gold-bearing MTs. In cell lines that overproduce MT, there is commonly a resistance to the cytotoxic effects of gold compounds. This resistance is also seen often in parent lines that have been repeatedly exposed to gold complexes. The mechanisms of resistance include but are not limited to enhanced biosynthesis of MT [102]. 

Linear gold complexes containing aminophenylphosphines such as 39 and 40 exhibit comparable cytotoxicity to cisplatin (193). These... 

Rush GF, Smith PF, Hoke GD, Alberts DW, Snyder RM, Mirabelli CK (1987) The mechanism of acute cytotoxicity of triethylphosphine gold complexes. II. Triethylphosphine gold chloride-induced alterations in mitochondrial function. Toxicol Appl Pharmacol 90 391 -00... 

Transmission electron microscopy (TEM) images showed that GNPs conjugated with Tat peptide (nuclear localization sequence) were mainly located in the nucleus of fibroblast and also revealed no appreciable cytotoxic effects [22]. In contrast, Tkachenko et al. functionalized GNPs with four different nuclear localization peptides ending with a Cys residue (which contains a free thiol) to evaluate the cellular trajectories of peptide gold complexes. Functionalized GNPs were... 

TABLE 5. Comparative cytotoxicity of gold complexes against CHO mammalian cells. Results are expressed as % survival... 

Trivalent gold complexes were potentially attractive as anticancer agents because of their cytotoxic effects on established human tumor cell lines. All tested Au+ complexes substantially retained their antitumor potency against platinum-resistant tumor cell lines for leukemia and ovarian cancer. Cytotoxicity of these compounds in vitro is attributed to binding with DNA and modification and subsequent impairment of replication and transcription processes. The paucity of data on Au+ complexes probably derives from their high redox potential and relatively poor stability, which makes their use problematical under physiological conditions. 

In 2011, a series of neutral gold complexes were synthesized by Gust and coworkers and their cytotoxicity was evaluated with MCF-7, MDAMB-231 breast cancer cell lines, and HT-29 and compared to cisplatin, aimmofin, and [Au(Cl)(PEt3)] (Figure 7.15 and Table 7.6) [16]. 

Nolan and coworkers reported the cytotoxicity of different neutral and cationic complexes. The first series of systems studied were Au-IPr derivatives bearing biocompatible moieties such as amino acids (L-proline or L-cysteine, Figure 7.16) [17]. In parallel, a second series of systems was selected, as it is well-known in the literature that cationic gold complexes can induce apoptosis of cancer cell lines. The IC50 were measured with LNCaP (prostate carcinoma) and MDA MB231 (breast carcinoma). 

Some dissociation of free phosphine is also observed in solution [97]. A relevant finding in this work is that the free phosphine is also active [95] (originally reported in 1966 [110]), and the implication is that the gold complex serves as a releasing mechanism for the cytotoxic ligand. Since copper salts potentiate the activity of free phosphine [111] there is a possibility of in vivo phosphine release followed by copper activation — similar in concept to the possible antitumour mechanisms of 1,10-phenan-throline and the thiosemicarbazones. In pursuit of this line, Cu(II) was shown to displace dppe from [Au(dppe)2]Cl [112] to give a Cu(I) complex. Further synthesis and testing of copper-diphosphine complexes struc-... 

Recently, Narain and co-workers synthesised cationic glycopolymer-based DTC conjugates using RAFT polymerisation and subsequent modification of pendant amine groups with carbon disulfide under basic conditions (Scheme 1.5). The resulting novel glycopolymer-DTC derivatives and their gold complexes were evaluated for their cytotoxicity profiles in a number of cell lines [109]. 

These complexes show considerable in vitro cytotoxic effects against various tumor cell lines [70, 71[. Moreover, the cationic complexes [Au(N,N, N")Cl[Cl are able to intercalate into ct DNA [71[. Gold(III) amidate complexes of histidine containing... 

Abbate, F., Orioli, P., Bruni, B., Marcon, G. and Messori, L. (2000) Crystal structure and solution chemistry of the cytotoxic complex 1,2-dichloro(o-phenanthroline) gold(III) chloride. Inorganica Chimica Acta, 311, 1. 

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