Gold amides as anticancer drugs: synthesis and activity studies

Newcombe, Sonya; Bobin, Mariusz; Shrikhande, Amruta; Gallop, Chris; Pace, Yannick; Yong, Helen; Gates, Rebecca; Chaudhuri, Shuvashri; Roe, S. Mark; Hoffmann, Eva R.; Viseux, Eddy M. E.

doi:10.1039/c3ob27460h

Cited by 15 publications

(16 citation statements)

References 25 publications

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“…Therefore, the development of a more robust approach would be desirable. In addition to the interesting reactivity shown by Toste and Bergman, Hoffman and Viseux have probed the anticancer properties of gold amide complexes, reacting modified triflamide compounds with phosphine-bearing gold chloride species [25]. Taking into account the interest in these type of complexes, we sought to use hydroxide 1 to develop an easy, green (in such deprotonation reactions, water is the sole byproduct) and straightforward methodology for the synthesis of gold(I)–amide complexes.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

Gómez‐Suárez¹,

Nelson²,

Thompson³

et al. 2013

Beilstein J. Org. Chem.

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A flexible, efficient and straightforward methodology for the synthesis of N-heterocyclic carbene gold(I)-amide complexes is reported. Reaction of the versatile building block [Au(OH)(IPr)] (1) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) with a series of commercially available (hetero)aromatic amines leads to the synthesis of several [Au(NRR')(IPr)] complexes in good yields and with water as the sole byproduct. Interestingly, these complexes present luminescence properties. UV-vis and fluorescence measurements have allowed the identification of their excitation and emission wavelengths (λ max ). These studies revealed that by selecting the appropriate amine ligand the emission can be easily tuned to achieve a variety of colors, from violet to green. 2216

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Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

Gómez‐Suárez¹,

Nelson²,

Thompson³

et al. 2013

Beilstein J. Org. Chem.

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“…In comparison to the two previously-discussed patents, their approach in using widely available amino acids, instead of organo-precursors, offers two advantages over C-donor ligands. First, contrary to, for example, NHCs ligands (strong σ-donor species), the Au-N bond may undergo ligand exchange; second, the considered synthetic approach can generate with high efficiency a large number of different structures usable in future drug development and orthogonal therapeutic strategies on multiple targets [73].…”

Section: Gold(i)-based Derivatives: Fields Of Application Structuresmentioning

confidence: 99%

“…Furthermore, both anticancer agents displayed comparable activity to Auranofin (reference drug) in the inhibition of the MDA-MB-231 cell line. Remarkably, the ligands alone induced no significant antiproliferative affect, thus featuring that the metal center plays a critical role in the cytotoxic activity [72,73]. Concerning the normal CV-1 cells, both compounds recorded higher IC 50 values (ca.…”

Section: Gold(i)-based Derivatives: Fields Of Application Structuresmentioning

confidence: 99%

Gold Complexes for Therapeutic Purposes: an Updated Patent Review (2010-2015)

Nardon¹,

Pettenuzzo²,

Fregona

2016

CMC

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Gold has always aroused great interest in the history of mankind. It has been used for thousands of years for jewelry, religious cult valuables, durable goods and in the art world. However, few know that such a precious and noble metal was exploited in the past by the ancients also for its therapeutic properties. More recently, in the twentieth century some complexes containing gold centers in the oxidation state +1 were studied for the treatment of the rheumatoid arthritis and the orally-administered drug Auranofin was approved by the FDA in 1985. From the chemical point of view, gold derivatives deserve special attention due to the unique position of this metal within the periodic table, which results in unconventional relativistic effects and, ultimately, in the highest electronegativity, electron affinity and redox potential among all metals. In this review, after an introduction concerning the use of gold complexes in medicine, we have examined all the patents internationally or nationally published in the years 2010-2015 (until December 31, 2015) and describing new inorganic compounds containing gold(I) and gold(III) with proved therapeutic properties. These patents were filed to mainly protect compounds with promising anticancer and anti-inflammatory activities (total 18 and 4, respectively). In particular, this work explores both coordination compounds containing ligands with various donor atoms (e.g., N-, O-, S- and -P) and organo-gold derivatives with at least one Au-C bond. The toxicological profile and the intracellular targets reported for some among the patented gold derivatives are discussed.

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“…The effect of stereochemistry on biological activity is of great importance in medicinal chemistry, as many of the biological targets are chiral [30,31]. The anticancer properties of chiral metal derivatives have been largely studied [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46], but the role of the stereochemistry in the biological activity of non-platinum based compounds has been less investigated [22,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61]. Effect of the absolute configuration on the anticancer efficiency of titanium compounds was firstly explored by Tshuva in 2010 [50].…”

Section: Introductionmentioning

confidence: 99%

Study of the anticancer properties of optically active titanocene oximato compounds

Cueva-Alique

Sierra

Pérez‐Redondo

et al. 2019

Journal of Organometallic Chemistry

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New water soluble and optically active cyclopentadienyl titanium derivatives [(η 5-C 5 H 5) 2 Ti{(1R,4S)-ĸON,(R)NH}Cl] (R = Bn (Benzyl) 1a', 2-pic (2-picolylamine) 1b') have been synthesized. The novel compounds along with those previously described [(η 5-C 5 H 5) 2 Ti{(1S,4R)-ĸON,(R)NH}Cl] (R = Bn 1a, 2-pic 1b) were evaluated by polarimetry, ultraviolet and circular dichroism spectroscopy. The structure of 1b was determined by single crystal X-ray crystallography and showed a unique terminal monohapto Ti-O disposition of the oximato ligand. All enantiomers have been tested against several cancer cell lines in vitro: prostate PC-3 and DU-145, lung A-549, pancreas MiaPaca-2, colorectal HCT-116, leukemia Jurkat and cervical HeLa. In addition, 1a, 1b and 1b' were tested against non-tumorigenic prostate RWPE-1 cell line. After 24 h of incubation, 1b and 1b' were moderately active against Jurkat and A-549 cells. The anti-proliferative effect of titanium compounds on prostate PC-3, DU-145 and RWPE-1 cell lines was also assessed after 72 h of drug exposure. The cytotoxic profile of the enantiomers was similar, exception made for the PC-3 cells, with S,R-isomers exhibiting cytotoxicities 2 to 3 times higher than R,S-compounds. Under these conditions, derivative 1b showed calculated IC 50 values better than those of Tacke´s Titanocene-Y (bis-[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride) on both the prostate PC-3 and DU-145 cells. 1a and 1b cytotoxic behaviour shows certain selectiveness, with activities 2-4 times lower on normal prostate RWPE-1 than on cancer PC-3 cells. Furthermore, 1b produces higher cytotoxicity on prostate PC-3, DU-145 and RWPE-1 cells than the additive dose of titanocene dichloride and pro-ligand b•HCl. Additionally, compound-DNA interactions have been investigated by equilibrium dialysis, Fluorescence Resonance Energy Transfer (FRET) melting assays and viscometric titrations, which suggest that these metal complexes and/or their hydrolysis products bind DNA either in the minor groove or externally. Highlights (85 characters) • Synthesis of novel enantiopure titanocene amino-oximato compounds is reported. • The X-ray crystal structure of one of the compounds shows a unique monohapto Ti-ON coordination. • One enantiomer shows IC 50 values lower than Titanocene-Y on both PC-3 and DU-145 cells. • One enantiomer is more active than additive doses of Ti(η 5-C 5 H 5)Cl 2 and oxime pro-ligand.

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Gold amides as anticancer drugs: synthesis and activity studies

Cited by 15 publications

References 25 publications

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

Synthesis, characterization and luminescence studies of gold(I)–NHC amide complexes

Gold Complexes for Therapeutic Purposes: an Updated Patent Review (2010-2015)

Study of the anticancer properties of optically active titanocene oximato compounds

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