Guided Antitumoural Drugs: (Imidazol‐2‐ylidene)(L)gold(I) Complexes Seeking Cellular Targets Controlled by the Nature of Ligand L

Bär, Sofia I.; Gold, Madeleine; Schleser, Sebastian W.; Rehm, Tobias; Bär, Alexander; Köhler, Leonhard H. F.; Carnell, Lucas R.; Biersack, Bernhard; Schobert, Rainer

doi:10.1002/chem.202005451

Cited by 10 publications

(12 citation statements)

References 71 publications

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“…They were also much more active than their chloridogold(I) precursors. Neutral chloridogold(I)–NHC complexes were often reported to be less anticancer active than analogous cationic NHC–gold(I) complexes [ 34 , 35 ]. Chloridogold–NHC complexes were casually developed as selective antiparasitic agents due to their relatively low toxicity to human cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

Schleser

Ghosh

Hörner

et al. 2023

IJMS

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Inspired by the vascular-disrupting agent combretastatin A-4 and recently published anticancer active N-heterocyclic carbene (NHC) complexes of Au(I), a series of new iodidogold(I)–NHC complexes was synthesized and characterized. The iodidogold(I) complexes were synthesized by a route involving van Leusen imidazole formation and N-alkylation, followed by complexation with Ag2O, transmetalation with chloro(dimethylsulfide)gold(I) [Au(DMS)Cl], and anion exchange with KI. The target complexes were characterized by IR spectroscopy, 1H and 13C NMR spectroscopy, and mass spectrometry. The structure of 6c was validated via single-crystal X-ray diffraction. A preliminary anticancer screening of the complexes using two esophageal adenocarcinoma cell lines showed promising nanomolar activities for certain iodidogold(I) complexes accompanied with apoptosis induction, as well as c-Myc and cyclin D1 suppression in esophageal adenocarcinoma cells treated with the most promising derivative 6b.

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Section: Discussionmentioning

confidence: 99%

New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

Schleser

Ghosh

Hörner

et al. 2023

IJMS

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“…Values are means ± SD of at least four independent experiments. Values marked with * were taken from Bär et al [33] EA.hy926…”

Section: Scheme 1 Synthesis Of Complexes 1-10mentioning

confidence: 99%

“…In addition, most tested complexes were of similar cytotoxicity against KB-V1 cervix carcinoma cells in the absence and presence of the Pgp-substrate verapamil, clinically used to re-sensitize resistant tumors [ 31 ]. This suggests that these complexes are not substrates of ABC-transporter-type efflux pumps [ 32 , 33 ].…”

Section: Biological Evaluationmentioning

confidence: 99%

Revisiting the anticancer properties of phosphane(9-ribosylpurine-6-thiolato)gold(I) complexes and their 9H-purine precursors

et al. 2022

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New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized, characterized, and evaluated in vitro for biological activities in comparison to related known purine complexes. By combining known anti-tumoral thio-purines with R3PAu moieties as present in auranofin, complexes with enhanced effects and selectivities were obtained, which not only act as cytostatics, but also disrupt tumor-specific processes. Their IC50 values in cytotoxicity test with tumor cell lines ranged from three-digit nanomolar to single-digit micromolar, revealing a tentative structure–activity relationship (SAR). Both the residues R2 of the phosphane ligand and R1 at C2 of the pyrimidine ring had a significant impact on the cytotoxicity. In most cases, the introduction of a ribo-furanosyl group at N9 of the purine led to a distinctly more cytotoxic complex. Most complexes were more active against multi-drug-resistant tumor cells or such lacking functional p53 when compared to the respective untreated wild type cell lines. Some nucleoside complexes displayed an interesting dose-dependent dual mode of action regarding cell cycle arrest and DNA repair mechanism. Some phosphane(purine-6-thiolato)gold (I) complexes had a stronger inhibitory effect on the thioredoxin reductase (TrxR) and on the reactive oxygen species (ROS) generation in cancer cells than is typical of other gold complexes. They also led to DNA fragmentation and showed anti-angiogenic effects. Their stability under test conditions was demonstrated by 77Se NMR monitoring of an exemplary selenopurine complex. Graphical abstract

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“…The MTT cell viability assay was conducted as described before. [37] Briefly, cells were seeded in 96-well microtiter plates (Sarstedt) with a cell density of 0.05 × 10 6 cells per ml with 100 µl per well and incubated for 24 h under standard cell culture conditions. Afterwards, a dilution series of test compounds was added, followed by a further incubation step for 72 h. A 0.05% in MTT in PBS solution was added (12.5 µl/well), followed by another incubation period of 2 h. Following a centrifugation step, the medium was discarded and 25 µl per well of SDS solution in DMSO (10% SDS, 0.6% AcOH in DMSO) were added, and plates were further incubated for 1 h. Absorbance was measured at 570 nm and 630 nm using a 4.2.5 | LDH release assay [28] HCT116 wt colon carcinoma cells were seeded in 96 well flat Means and SD were calculated from at least three independent experiments.…”

Section: Mtt Cell Viability Assaymentioning

confidence: 99%

New chimeric HDAC inhibitors for the treatment of colorectal cancer

Bär

Pradhan²,

Biersack

et al. 2022

Archiv der Pharmazie

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Colorectal cancer is the third most common cause of cancer-associated deaths due to a high recurrence rate and an increasing occurrence of resistance to established therapies. This highlights the importance of developing new chemotherapeutic agents. The current study focuses on cancer-specific targets such as apoptosisinhibiting survivin, which distinguishes cancer cells from healthy tissue. A combination of pharmacophores of established anticancer agents to afford chimeric pleiotropic chemotherapeutic agents was tested on this cancer entity. We analysed the effects of the dual mode anticancer agents, animthioxam, brimbam, troxbam, and troxham, as well as their structural congeners suberoylanilide hydroxamic acid and combretastatin A-4 on human cancer cell lines. Their cytotoxicity was determined using the MTT assay, further techniques for detecting apoptotic events, cell cycle analyses, clonogenic and wound healing assays, immunostaining, histone deacetylase (HDAC) activity measurements, and Western blot analysis for the detection of survivin expression in HCT116 colon cancer cells. Molecular docking studies were conducted to assess potential molecular targets of the test compounds.The test compounds were found selectively cytotoxic toward cancer cells by inducing apoptosis. The metastatic potential was effectively reduced by disruption of the microtubular cytoskeleton. The test compounds were also proven to be general HDAC inhibitors and to lead to reduced survivin expression.

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Guided Antitumoural Drugs: (Imidazol‐2‐ylidene)(L)gold(I) Complexes Seeking Cellular Targets Controlled by the Nature of Ligand L

Cited by 10 publications

References 71 publications

New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

New 4,5-Diarylimidazol-2-ylidene–iodidogold(I) Complexes with High Activity against Esophageal Adenocarcinoma Cells

Revisiting the anticancer properties of phosphane(9-ribosylpurine-6-thiolato)gold(I) complexes and their 9H-purine precursors

New chimeric HDAC inhibitors for the treatment of colorectal cancer

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