Exploring the Reactivity and Biological Effects of Heteroleptic N‐Heterocyclic Carbene Gold(I)‐Alkynyl Complexes

Oberkofler, Jens; Bonsignore, Riccardo; Pöthig, Alexander; Platts, James Alexis; Casini, Angela; Kühn, Fritz E.

doi:10.1002/ejic.201901043

Cited by 30 publications

(30 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study aims at extending the investigation to different families of Au I and Au III compounds to identify possible structure–activity relationships. Thus, nine gold compounds, previously characterized for their anticancer effects, were synthesized according to reported procedures, including Au I mono‐ and bis‐NHC complexes ( 1 – 4 ), [23–25] Au III complexes coordinated to a bidentate

N^{\land} N

scaffold ( 5 , 6 ), [26,27,28] and three cyclometallated Au III complexes with

C^{\land} N

ligands ( 7 – 9 ) [29,30,31] (Figure 1).…”

Section: Figurementioning

confidence: 99%

Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

et al. 2020

Self Cite

View full text Add to dashboard Cite

A series of mononuclear coordination or organometallic Au I /Au III complexes (1-9) have been comparatively studied in vitro for their antileishmanial activity against promastigotes and amastigotes, the clinically relevant parasite form, of Leishmania amazonensis and Leishmania braziliensis. One of the cationic Au I bis-N-heterocyclic carbenes (3) has low EC 50 values (ca. 4 μM) in promastigotes cells and no toxicity in host macrophages. Together with two other Au III complexes (6 and 7), the compound is also extremely effective in intracellular amastigotes from L. amazonensis. Initial mechanistic studies include an evaluation of the gold complexes' effect on L. amazonensis' plasma membrane integrity. Leishmaniasis is a vector-borne disease caused by Leishmania protozoan parasites that leads to cutaneous (localized, mucosal, diffuse, disseminated) or visceral manifestations, depending on the species, immune status of the host and geographic distribution. [1] Leishmania amazonensis and Leishmania braziliensis are important species related to cutaneous leishmaniasis in the New World, especially in Brazil, where about 73k to 120k people are infected every year. [2] While vaccines for humans are not available, antimony-based compounds, such as sodium stibogluconate (Pentostam®, Figure 1), amphotericin B (AMB), paromomycin, miltefosine, and pentamidine have been used for treating patients for several decades, despite their severe side effects and long-term parenteral administration in the majority of the cases. [3] In this context, a key area in [a

show abstract

N^{\land} N

scaffold ( 5 , 6 ), [26,27,28] and three cyclometallated Au III complexes with

C^{\land} N

ligands ( 7 – 9 ) [29,30,31] (Figure 1).…”

Section: Figurementioning

confidence: 99%

Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…As seen in other NHC-Au-acetylides, the bond between the gold atom and the alkynyl ligand of 5a – 5e is slightly shorter than that to the carbene, however still within the margins of acceptable Au-C bond lengths [ 14 ]. The C-C bond lengths of the alkyne (C 30 -C 31 ) in the 1.193(6)–1.217(7) Å range are characteristic of a triple bond [ 27 ].…”

Section: Resultsmentioning

confidence: 96%

“…Interestingly, an iodido analogue of auranofin was shown to exhibit greater cytotoxicity than both auranofin and cisplatin against the human ovarian cancer cell line A2780 [ 12 ]. Alkynes are another ligand class often seen in gold(I) complexes, however only a handful of NHC-gold(I)-acetylides synthesised have been tested for their biological properties [ 13 , 14 , 15 ]. Mostly, gold(I)-acetylides are studied for their photophysical properties [ 16 ], although there are examples of phosphine-gold(I)-acetylides displaying high cytotoxicity against selected cancer cell lines [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A

et al. 2020

View full text Add to dashboard Cite

N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br−, I−, C≡C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.

show abstract

“…[6][7][8] Different classes of Au complexes have been evaluated to date; (i) neutral linear auranofin-type phosphane complexes, (ii) tetrahedral cationic Au(I) phosphane complexes, usually containing chelating bis(phosphane) ligands, (iii) linear Au(I) N-heterocyclic carbene (NHC) complexes and (iv) squareplanar Au(III) complexes. [9][10][11][12][13][14][15][16][17][18] Recently a few [Au(I)(alkynyl) (phosphane)] complexes have been reported that showed promising in vitro and in vivo activities, although their number has remained small compared to other gold complexes. [19][20][21][22][23] Here we report alkynyl phosphane and alkynyl NHC Au(I) complexes where the alkynyl ligand is a derivative of the quinazoline carboxamide class of ligands that bind to the translocator protein 18 kDa (TSPO).…”

Section: Introductionmentioning

confidence: 99%

“…Calc. (%) for C18 H 13 N 3 O (287.10): C, 75.25; H, 4.56; N, 14.63. Found (%): C, 75.20; H, 4.55; N, 14.59.…”

mentioning

confidence: 99%

Gold(I) Complexes with a Quinazoline Carboxamide Alkynyl Ligand: Synthesis, Cytotoxicity, and Mechanistic Studies

et al. 2021

View full text Add to dashboard Cite

A series of gold(I) complexes with the general formula [Au-(L2)(L')] (L2 = 4-phenyl-N-(prop-2-yn-1-yl)quinazoline-2-carboxamide, L' = PPh 3 (triphenylphosphine), 1; TPA (1,3,5-triaza-7phosphaadamantane), 2, and Me 2 -imy (1,3-dimethylimidazol-2ylidene), 3) were synthesized and fully characterized by spectroscopic methods. The alkynyl ligand L2 belongs to the quinazoline carboxamide class of ligands that are known to bind to the translocator protein (TSPO) at the outer mitochon-drial membrane. 1 and 2 exert cytotoxic effects in bladder cancer cells with IC 50 values in the low micromolar range. Further mechanistic analysis indicated that the two complexes both act by inducing reactive oxygen species and caspasemediated apoptosis. The complexes inhibit thioredoxin reductase, an established target of anticancer gold(I) complexes. Docking studies confirmed that after ligand exchange the free ligand L2 can interact with the TSPO binding site.

show abstract

Exploring the Reactivity and Biological Effects of Heteroleptic N‐Heterocyclic Carbene Gold(I)‐Alkynyl Complexes

Cited by 30 publications

References 72 publications

Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

Comparing the Antileishmanial Activity of Gold(I) and Gold(III) Compounds in L. amazonensis and L. braziliensis in Vitro

Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A

Gold(I) Complexes with a Quinazoline Carboxamide Alkynyl Ligand: Synthesis, Cytotoxicity, and Mechanistic Studies

Contact Info

Product

Resources

About