The anticancer activity of an air-stable Pd(<scp>i</scp>)-NHC (NHC = N-heterocyclic carbene) dimer

Scattolin, Thomas; Bortolamiol, Enrica; Palazzolo, Stefano; Caligiuri, Isabella; Perin, Tiziana; Canzonieri, Vincenzo; Demitri, Nicola; Rizzolio, Flavio; Cavallo, Luigi; Dereli, Büşra; Mane, Manoj V.; Nolan, Steven P.; Visentin, Fabiano

doi:10.1039/d0cc03883k

Cited by 41 publications

(17 citation statements)

References 50 publications

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“…As shown in Table 1, the organometallic cages [Ag 4 (2) 2 ](OTf) 4 and [Au 4 (2) 2 ](OTf) 4 show considerable anticancer activity with the half maximal inhibitory concentration (IC 50 ) values ranging from 2.271 to 3.887 μM and 1.667 to 2.272 μM, respectively, which were similar or even more potent to those of cisplatin in some cancer cell lines (Supporting Information Table S3). [74][75][76] In addition, the relatively high IC 50 values of [Ag 4 (2) 2 ] (OTf) 4 and [Au 4 (2) 2 ](OTf) 4 toward L-02 cells indicate that they have relatively low toxicity to human normal hepatocyte cells (Table 1). To our knowledge, this represents the first example of TPE-based organometallic cages used for cell imaging and treatment of cancer cells.…”

Section: Mechanochromic Propertiesmentioning

confidence: 99%

Multistimuli-Responsive Fluorescent Organometallic Assemblies Based on Mesoionic Carbene-Decorated Tetraphenylethene Ligands and Their Applications in Cell Imaging

Yang

et al. 2022

CCS Chem

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The controllable construction of light-emitting organometallic supramolecular materials integrating stimulus responses and biological applications is still a major challenge today. In this work, emissive organometallic assemblies based on Ag I /Au I and mesoionic carbene-decorated tetraphenylethene (MIC-TPE) ligands have been synthesized and characterized. Photophysical studies showed that these organometallic assemblies [M 4 (2) 2 ](OTf) 4 not only fluoresce in various dilute solutions, resulting from the rigidification of MIC-TPE ligands upon complexation, but also show tunable fluorescence wavelengths and intensity behaviors in mixed solvent systems and at varying temperatures while in solution, and mechanical pressure stimulus-responsive fluorescent features in the solid state. Furthermore, the organometallic cages [M 4 (2) 2 ](OTf) 4 (M = Ag and Au) were successfully employed for cell imaging and showed the potential of anticancer activity, making them promising candidates for cancer theranostics. This work provides a simple and efficient method to prepare highly emissive and stimulus-responsive organometallic materials and paves the way for related biological applications such as cancer cell imaging and targeted therapy.

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Section: Mechanochromic Propertiesmentioning

confidence: 99%

Multistimuli-Responsive Fluorescent Organometallic Assemblies Based on Mesoionic Carbene-Decorated Tetraphenylethene Ligands and Their Applications in Cell Imaging

Yang

et al. 2022

CCS Chem

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“…In this paper, we aimed to evaluate and compare the toxicity of two long and two short-chain PFASs toxicity in a physiological relevant and innovative liver mini-organs (organoids) at cellular level by measuring cell viability, structural histology and enzymatic activity. Organoids are 3D models that can recapitulate in vitro the physiology of organs and represent a platform in which it is possible to predict the effects of a compound more rapidly than in vivo [27][28][29][30][31]. Two long-chain (PFOS, PFOA) and two short-chain PFAS (HFBA: Heptafluorobutyric acid also known as perfluorobutyric acid; PFPA: Pentafluoropropionic anhydride) were tested.…”

Section: Introductionmentioning

confidence: 99%

Early Warnings by Liver Organoids on Short- and Long-Chain PFAS Toxicity

Palazzolo

Caligiuri

Sfriso

et al. 2022

Toxics

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Short-chain per-fluoroalkyl substances (PFAS) have replaced long-chains in many applications, however the toxicity and its mode of action and interactions due to the large number of these compounds and their mixtures is still poorly understood. The paper aims to compare the effects on mouse liver organoids (target organ for bioaccumulation) of two long-chain PFAS (perfluorooctane sulfonate -PFOS-, perfluorooctanoic acid -PFOA) and two short-chain PFAS commonly utilized in the industry (heptafluorobutyric acid -HFBA-, Pentafluoropropionic anhydride-PFPA) to identify the mode of action of these classes of contaminants. Cytomorphological aberrations and ALT/GDH enzyme disruption were identified but no acute toxicity endpoint neither apoptosis was detected by the two tested short-chain PFAS. After cytomorphological analysis, it is evident that short-chain PFAS affected organoid morphology inducing a reduction of cytostructural complexity and aberrant cytological features. Conversely, EC50 values of 670 ± 30 µM and 895 ± 7 µM were measured for PFOS and PFOA, respectively, together with strong ALT/GDH enzyme disruption, caspase 3 and 7 apoptosis activation and deep loss of architectural complexity of organoids in the range of 500–1000 µM. Eventually, biochemical markers and histology analysis confirmed the sensitivity of organoid tests that could be used as a fast and reproducible platform to test many PFAS and mixtures saving time and at low cost in comparison with in vivo tests. Organoids testing could be introduced as an innovative platform to assess the toxicity to fast recognize potentially dangerous pollutants.

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“…It has been recently reported that organometallic Pd(0) derivatives containing purine-based N-heterocyclic carbenes exert significant antiproliferative activity against ovarian cancer cell lines, comparable to cisplatin even in resistant cell lines [ 211 ]. Moreover, following an evolution of Pd-based derivatives from the more common Pd(II) complexes to the Pd(0) ones, Scattolin and co-workers reported in 2020 about high and selective antiproliferative activity on different cancer cell lines and advanced preclinical ovarian cancer models of an original dinuclear Pd(I)-based complex, showing mechanisms of action different from that of cisplatin and mainly involving mitochondria [ 212 ]. These findings could pave the way towards the discovery of new alternatives among organopalladium derivatives endowed with antiproliferative action.…”

Section: Palladiummentioning

confidence: 99%

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

et al. 2022

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Countless expectations converge in the multidisciplinary endeavour for the search and development of effective and safe drugs in fighting cancer. Although they still embody a minority of the pharmacological agents currently in clinical use, metal-based complexes have great yet unexplored potential, which probably hides forthcoming anticancer drugs. Following the historical success of cisplatin and congeners, but also taking advantage of conventional chemotherapy limitations that emerged with applications in the clinic, the design and development of non-platinum metal-based chemotherapeutics, either as drugs or prodrugs, represents a rapidly evolving field wherein candidate compounds can be fine-tuned to access interactions with druggable biological targets. Moving in this direction, over the last few decades platinum family metals, e.g., ruthenium and palladium, have been largely proposed. Indeed, transition metals and molecular platforms where they originate are endowed with unique chemical and biological features based on, but not limited to, redox activity and coordination geometries, as well as ligand selection (including their inherent reactivity and bioactivity). Herein, current applications and progress in metal-based chemoth are reviewed. Converging on the recent literature, new attractive chemotherapeutics based on transition metals other than platinum—and their bioactivity and mechanisms of action—are examined and discussed. A special focus is committed to anticancer agents based on ruthenium, palladium, rhodium, and iridium, but also to gold derivatives, for which more experimental data are nowadays available. Next to platinum-based agents, ruthenium-based candidate drugs were the first to reach the stage of clinical evaluation in humans, opening new scenarios for the development of alternative chemotherapeutic options to treat cancer.

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The anticancer activity of an air-stable Pd(i)-NHC (NHC = N-heterocyclic carbene) dimer

Abstract: A new dinuclear Pd(I) complex coordinating two bis(NHC) ligands revealed an unsuspected stability despite the unsaturation of the two metal centres. Even more surprisingly, the compound showed a high and...

Cited by 41 publications

References 50 publications

Multistimuli-Responsive Fluorescent Organometallic Assemblies Based on Mesoionic Carbene-Decorated Tetraphenylethene Ligands and Their Applications in Cell Imaging

Multistimuli-Responsive Fluorescent Organometallic Assemblies Based on Mesoionic Carbene-Decorated Tetraphenylethene Ligands and Their Applications in Cell Imaging

Early Warnings by Liver Organoids on Short- and Long-Chain PFAS Toxicity

Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics

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