1. Designing an anticancer Pd(II) complex as poly(ADP-ribose) polymerase 1 inhibitor.
1. 设计抗癌 Pd ( II ) 复合物作为聚 ( ADP - 核糖 ) 聚合酶 1 抑制剂。
期刊:International journal of biological macromolecules
日期:2025-01-14
DOI :10.1016/j.ijbiomac.2025.139885
Targeting DNA repair mechanisms, particularly PARP-1 inhibition, has emerged as a promising strategy for developing anticancer therapies. we designed and synthesized two 2-thiazolecarboxaldehyde thiosemicarbazone palladium(II) complexes (C1 and C2), and evaluated their anti-cancer activities. These Pd(II) complexes exhibited potent PARP-1 enzyme inhibition and demonstrated considerable antiproliferative activity against various cancer cell lines. In vivo studies using the A549 tumor xenograft model revealed that C2 effectively suppressed tumor growth and exhibited minimal systemic toxicity. Mechanistically, C2 induced A549 cell death through multiple pathways: cell cycle arrest, elevated intracellular reactive oxygen species (ROS) levels, DNA damage induction, exacerbated DNA double-strand breakage via PARP-1 inhibition, mitochondrial membrane potential reduction, and ultimately apoptosis. These findings provide a new design strategy for developing safe and highly effective PARP-1 inhibitors.
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1区Q1影响因子: 16.9
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2. Ligand-Protected Golden Fullerene Au with Unprecedented Metal Coordination Number of 15.
2. 配体保护的金富勒烯 Au42 , 具有前所未有的金属配位数为 15 。
期刊:Angewandte Chemie (International ed. in English)
日期:2024-12-23
DOI :10.1002/anie.202417904
A golden fullerene with a composition of [Au(PhP)(5-CF-Hpa)] (CFCOO) (5-CF-Hpa=5-trifluoropyridyl-2-amine) (Au) has been synthesized with pyridylamino and phosphine ligands as the protecting agents. Single crystal X-ray structural analysis reveals that the cluster has a D Au core, which can be depicted as a centered core-shell structure Au@Au@Au. The 41 Au atoms of the Au@Au core-shell can be derived from placing a gold atom in the center of each polygon of C (D). Surprisingly, the centered gold atom of this noble cluster has the highest coordination number in metal nanoclusters of 15. Quantum-chemical studies suggest that the excellent stability of Au results from both the superatomic characteristics of the Au kernel and the gold-ligand interactions.
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1区Q1影响因子: 15.6
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3. Increasing the Cytotoxicity of Ru(II) Polypyridyl Complexes by Tuning the Electronic Structure of Dioxo Ligands.
3. 通过调整二氧杂配体的电子结构来提高Ru(II)聚吡啶基配合物的细胞毒性。
作者:Notaro Anna , Jakubaszek Marta , Rotthowe Nils , Maschietto Federica , Vinck Robin , Felder Patrick S , Goud Bruno , Tharaud Mickaël , Ciofini Ilaria , Bedioui Fethi , Winter Rainer F , Gasser Gilles
期刊:Journal of the American Chemical Society
日期:2020-03-17
DOI :10.1021/jacs.9b12464
Due to the great potential expressed by an anticancer drug candidate previously reported by our group, namely, Ru-sq ([Ru(DIP)(sq)](PF) (DIP, 4,7-diphenyl-1,10-phenanthroline; sq, semiquinonate ligand), we describe in this work a structure-activity relationship (SAR) study that involves a broader range of derivatives resulting from the coordination of different catecholate-type dioxo ligands to the same Ru(DIP) core. In more detail, we chose catechols carrying either an electron-donating group (EDG) or an electron-withdrawing group (EWG) and investigated the physicochemical and biological properties of their complexes. Several pieces of experimental evidences demonstrated that the coordination of catechols bearing EDGs led to deep-red positively charged complexes - in which the preferred oxidation state of the dioxo ligand is the uninegatively charged semiquinonate. Complexes and , on the other hand, are blue/violet neutral complexes, which carry an EWG-substituted dinegatively charged catecholate ligand. The biological investigation of complexes - led to the conclusion that the difference in their physicochemical properties has a strong impact on their biological activity. Thus, complexes - expressed much higher cytotoxicities than complexes and . Complex constitutes the most promising compound in the series and was selected for a more in depth biological investigation. Apart from its remarkably high cytotoxicity (IC = 0.07-0.7 μM in different cancerous cell lines), complex was taken up by HeLa cells very efficiently by a passive transportation mechanism. Moreover, its moderate accumulation in several cellular compartments (i.e., nucleus, lysosomes, mitochondria, and cytoplasm) is extremely advantageous in the search for a potential drug with multiple modes of action. Further DNA metalation and metabolic studies pointed to the direct interaction of complex with DNA and to the severe impairment of the mitochondrial function. Multiple targets, together with its outstanding cytotoxicity, make complex a valuable candidate in the field of chemotherapy research. It is noteworthy that a preliminary biodistribution study on healthy mice demonstrated the suitability of complex for further in vivo studies.
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1区Q1影响因子: 15.6
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4. Phenazine Cations as Anticancer Theranostics.
4. 吩嗪阳离子作为抗癌热解剖学。
期刊:Journal of the American Chemical Society
日期:2024-04-29
DOI :10.1021/jacs.4c03491
The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.
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1区Q1影响因子: 15.7
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5. The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system.
5. AUTOTAC化学生物学平台目标蛋白质降解通过自噬溶酶体系统。
期刊:Nature communications
日期:2022-02-16
DOI :10.1038/s41467-022-28520-4
Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated into oligomeric bodies in complex with targets for their sequestration and degradation. We use AUTOTACs to degrade various oncoproteins and degradation-resistant aggregates in neurodegeneration at nanomolar DC values in vitro and in vivo. AUTOTAC provides a platform for selective proteolysis in basic research and drug development.
期刊:Angewandte Chemie (International ed. in English)
日期:2024-10-30
DOI :10.1002/anie.202412585
Despite significant improvements in the treatment of cancerous tumors in the last decades, cancer remains one of the deadliest diseases worldwide. To overcome the shortcomings of currently applied chemotherapeutic treatments, much research efforts have been devoted towards the development of ferroptosis inducing anticancer agents. Ferroptosis is a newly described form of regulated, non-apoptotic cell death that is associated with high potential inside the clinics. Herein, the chemical synthesis and biological evaluation of a Co(III) polypyridine sulfasalazine complex as a ferroptosis inducer is reported. Upon entering the cancerous cells, the metal complex primarily accumulated in the mitochondria, triggering the production of hydroxy radicals and lipid peroxides, ultimately causing cell death by ferroptosis. The compound demonstrated to eradicate various monolayer cancer cells as well as colon carcinoma multicellular tumor spheroids. To the best of our knowledge this study reports on the first example of a Co(III) complex that is capable of inducing ferroptosis.
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1区Q1影响因子: 5.5
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7. Partial to Total Generation of 3D Transition-Metal Complexes.
7. 部分至全部产生 3D 过渡金属配合物。
期刊:Journal of chemical theory and computation
日期:2024-09-09
DOI :10.1021/acs.jctc.4c00775
The design of transition-metal complexes (TMCs) has drawn much attention over the years because of their important applications as metallodrugs and functional materials. In this work, we present an extension of our recently reported approach, LigandDiff [Jin et al. , 4377(2024)]. The new model, which we call multi-LigandDiff, is more flexible and greatly outperforms its predecessor. This scaffold-based diffusion model allows de novo ligand design with either existing ligands or without any ligand. Moreover, it allows users to predefine the denticity of the generated ligand. Our results indicate that multi-LigandDiff can generate well-defined ligands and is transferable to multiple transition metals and coordination geometries. In terms of its application, multi-LigandDiff successfully designed 338 Fe(II) spin-crossover (SCO) complexes from only 47 experimentally validated SCO complexes. And these generated complexes are configurationally diverse and structurally reasonable. Overall, the results show that multi-LigandDiff is an ideal tool to design novel TMCs from scratch.
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1区Q1影响因子: 16.9
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8. High-Throughput Combinatorial Metal Complex Synthesis.
8. 高通量组合金属配合物合成。
期刊:Angewandte Chemie (International ed. in English)
日期:2025-01-10
DOI :10.1002/anie.202420204
High-throughput combinatorial metal complex synthesis has emerged as a powerful tool for rapidly generating and screening diverse libraries of metal complexes, enabling accelerated discovery in fields such as catalysis, medicinal chemistry, and materials science. By systematically combining building blocks under mild and efficient conditions, researchers can explore broad chemical spaces, increasing the likelihood of identifying complexes with desired properties. This method streamlines hit identification and optimisation, especially when integrated with high-throughput screening and data-driven approaches like machine learning. Despite challenges such as scalability and purity control, recent advancements in automation and predictive modelling are enhancing the efficiency of combinatorial synthesis, opening new avenues for the development of metal-based catalysts, therapeutic agents, and functional materials.
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1区Q1影响因子: 6.8
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9. Recent Advances of Metal Complexes in the Treatment of Hepatocellular Carcinoma.
9. 金属配合物治疗肝癌的研究进展.
期刊:Journal of medicinal chemistry
日期:2024-12-16
DOI :10.1021/acs.jmedchem.4c01850
Chemotherapy has long been used in the clinical management of hepatocellular carcinoma (HCC), driving the development of anticancer chemotherapy drugs. Platinum complexes have attracted significant attention and have led to the creation of a series of platinum-based drugs used in diverse cancer treatments, including HCC. However, the clinical use of platinum drugs faces critical challenges due to drug resistance and side effects. Consequently, ongoing efforts have been devoted to the continuous development of new metal complexes with antitumor properties, aiming to serve as effective alternatives for HCC treatment. In this Perspective, we summarize and highlight the progress and relevant mechanisms related to new metal complexes in the treatment of HCC over the past decade. The development of metal complexes has the potential to further expand the scope of chemotherapy applications for HCC.
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1区Q1影响因子: 11.5
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10. Channel-assembling tumor microenvironment on-chip for evaluating anticancer drug efficacy.
10. 用于评估抗癌药物疗效的芯片上通道组装肿瘤微环境。
期刊:Journal of controlled release : official journal of the Controlled Release Society
日期:2024-11-24
DOI :10.1016/j.jconrel.2024.11.030
Organ-on-a-chip is an advanced system for evaluating drug response in diseases. It simulates the in vivo tumor microenvironment, aiding in the understanding of drug mechanisms and tumor responses. It mimics the structure of the tumor microenvironment and the dynamic conditions within the body. As a result, it holds the potential for applications in precision and personalized medicine. However, there are still limitations in sequential development processes and complex structures, resulting in time-consuming molecular interference during system development. In this study, we developed a channel-assembling tumor microenvironment-on-chip (CATOC) system to overcome these limitations. CATOC was easily segmented into blood vessels and a tumor microenvironment-on-chip, which can be independently developed. The tumor microenvironment-on-chip consists of two independent channels for evaluating drug responses in different types of tumor microenvironments. Each fully developed system was physically interconnected to create a CATOC. Interconnected CATOC was used to validate chemical and targeted anticancer drug responses in different subtypes of the breast tumor microenvironment. We also emphasized the significance of on-chip experiments by observing the drug response of tumor spheroids on CATOC and scaffold-free platforms.
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1区Q1影响因子: 26.8
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11. Self-Assembled Metal Complexes in Biomedical Research.
11. 自组装金属配合物在生物医学研究中的应用。
期刊:Advanced materials (Deerfield Beach, Fla.)
日期:2024-12-23
DOI :10.1002/adma.202416122
Cisplatin is widely used in clinical cancer treatment; however, its application is often hindered by severe side effects, particularly inherent or acquired resistance of target cells. To address these challenges, an effective strategy is to modify the metal core of the complex and introduce alternative coordination modes or valence states, leading to the development of a series of metal complexes, such as platinum (IV) prodrugs and cyclometalated complexes. Recent advances in nanotechnology have facilitated the development of multifunctional nanomaterials that can selectively deliver drugs to tumor cells, thereby overcoming the pharmacological limitations of metal-based drugs. This review first explores the self-assembly of metal complexes into spherical, linear, and irregular nanoparticles in the context of biomedical applications. The mechanisms underlying the self-assembly of metal complexes into nanoparticles are subsequently analyzed, followed by a discussion of their applications in biomedical fields, including detection, imaging, and antitumor research.
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1区Q1影响因子: 6.8
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12. Tailored Metal-Based Catalysts: A New Platform for Targeted Anticancer Therapies.
12. 定制的金属基催化剂 : 靶向抗癌治疗的新平台。
期刊:Journal of medicinal chemistry
日期:2024-09-30
DOI :10.1021/acs.jmedchem.4c01680
Innovative strategies for targeted anticancer therapies have gained significant momentum, with metal complexes emerging as tunable catalysts for more effective and safer treatments. Rational design and engineering of metal complexes enable the development of tailored molecular structures optimized for precision oncology. The strategic incorporation of metal complex catalysts within combinatorial therapies amplifies their anticancer properties. This perspective highlights the advancements in synthetic strategies and rational design since 2019, showing how tailored metal catalysts are optimized by designing structures to release or synthesize active drugs, leveraging the target-specific characteristics to develop more precise cancer therapies. This review explores metal-based catalysts, including those conjugated with biomolecules, nanostructures, and metal-organic frameworks (MOFs), highlighting their catalytic activity in biological environments and their / performance. To sum up, the potential of metal complexes as catalysts to reshape the landscape of anticancer therapies and foster novel avenues for therapeutic advancement is emphasized.