Ruthenium Complex HB324 Induces Apoptosis via Mitochondrial Pathway with an Upregulation of Harakiri and Overcomes Cisplatin Resistance in Neuroblastoma Cells In Vitro

Wilke, Nicola L.; Burmeister, Hilke; Frias, Corazon; Ott, Ingo; Prokop, Aram

doi:10.3390/ijms24020952

Cited by 11 publications

(3 citation statements)

References 65 publications

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“…Ruthenium complex HB324 has been shown to effectively inhibit the proliferation of leukemia cells in a dose-dependent manner. At a concentration of 1 µM, HB324 caused 100% proliferation inhibition, indicating its potential as an effective anti-proliferative agent [16].…”

Section: Discussionmentioning

confidence: 98%

Evaluation of the Potential Cytotoxicity of Ruthenium Complex Ii Against U-373 Glioblastoma Cells

J. SAADH,

AL-WAHISH

2023

Int J App Pharm

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Objective: The potential of ruthenium complexes as anticancer agents has gained significant attention in the scientific community. The aim of this study was to investigate the effect of dithiocyanato-N-bis[8(diphenylphosphino)quinoline]ruthenium (II), [Ru(N-P)2(NCS)2] on the glioblastoma U-373 tumor cells and apoptosis. Methods: Ru(N-P)2(NCS)2] was synthesized and characterized using FTIR, and X-ray crystallography. The cytotoxic effects of [Ru(N-P)2(NCS)2] on glioblastoma U-373 tumor cells were evaluated using both the trypan blue assay and the activity of caspase-3 to detect apoptosis. A DPPH scavenging assay was used to evaluate the antioxidant activity. Results: The [Ru(N-P)2(NCS)2] complex effectively inhibited the glioblastoma U-373 tumor cells with an IC50 of ~ 23 µg/ml. Similar to the majority of chemotherapeutic agents that kill via the intrinsic pathway, [Ru(N-P)2(NCS)2] induces apoptosis, which was confirmed by the activation of caspase-3, and these effects were dose-dependent. Ruthenium has antioxidant properties, so ruthenium Complex II exhibits lower toxicity towards normal cells while effectively targeting and eliminating cancer cells. Conclusion: [Ru(N-P)2(NCS)2] is considered promising for researchers investigating putative biological activities, particularly antitumor and immune-related activity.

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Section: Discussionmentioning

confidence: 98%

Evaluation of the Potential Cytotoxicity of Ruthenium Complex Ii Against U-373 Glioblastoma Cells

J. SAADH,

AL-WAHISH

2023

Int J App Pharm

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“…The millimeter dimensions of the resulting inhibitory zones were used as a benchmark for anti‐microbial activity. As a negative control, solvent controls (DMSO) were included in all experiments [45] . The investigated compounds were dissolved in DMSO, which showed no inhibitory zone, confirming that it has no effect on the development of the observed bacteria and fungi.…”

Section: Methodsmentioning

confidence: 94%

Facile Synthesis of Benzimidazoles via Oxidative Cyclization of Acyclic Monoterpene Aldehyde with Diamines: Studies on Antimicrobial and in Vivo Evaluation of Zebrafish

Vaithiyalingam,

Mohan Kumar,

Kamaraj

et al. 2023

Chemistry & Biodiversity

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Citral (1a), a bioactive component of Cymbopogon citratus (lemongrass) could be isolated and semi‐synthetic analogs synthesized with improved therapeutic properties. Herein we first report describes citral (1a) as a primary material for the synthesis of benzimidazole derivatives between various o‐phenylenediamines (2a–l) in the presence of Diisopropylethylamine (DIPEA) as a commercially available environmentally benign base, ethanol as a green solvent and the yield of all benzimidazole derivatives (3a–l) was between 68–76 %; The semi‐synthetically prepared benzimidazole derivatives (3a–l) were assessed for their anti‐bacterial and anti‐fungal properties. The benzimidazole compounds (3a–b, and 3g–j) exhibit good anti‐microbial activity. In addition, in silico study was carried out to determine the specific binding affinity of the diamine halogen substituted benzimidazole derivatives to the specific target proteins. In silico analysis revealed a high correlation between docking results and experimental results. Finally, benzimidazole demonstrated significant antibacterial and antifungal activity. Zebrafish embryos were subjected to In vivo toxicological test found that all of the benzimidazole compounds (3a–l) were non‐toxic and had low embryotoxicity after 96 h, with an LC50 of 36.425 μg, which could facilitate the design of novel antimicrobial agents using a cost‐effective method.

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“…substituted with methyl on benzimidazole ring was found to efficiently activate Harakiri (HRK), a proapoptotic protein from the Bcl-2 family that interacts with and inhibits the antiapoptotic and death-repressor proteins Bcl-2 and Bcl-xl, thereby promoting apoptosis. 68 Furthermore, the authors also demonstrated that Rh(I)-NHC complex 5, which contains a naphthalimide moiety, can induce apoptosis in Nalm-6 cells through the mitochondrial pathway.…”

Section: Target Bcl-2 Familymentioning

confidence: 97%

A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

Zhao,

Han,

Peng

et al. 2024

Medicinal Research Reviews

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Metal complexes based on N‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal–NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal–NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal–NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal–NHC complexes that trigger apoptotic cell death via different apoptosis‐related targets or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal–NHC complexes to elucidate their emerging application in medicinal chemistry.

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Ruthenium Complex HB324 Induces Apoptosis via Mitochondrial Pathway with an Upregulation of Harakiri and Overcomes Cisplatin Resistance in Neuroblastoma Cells In Vitro

Cited by 11 publications

References 65 publications

Evaluation of the Potential Cytotoxicity of Ruthenium Complex Ii Against U-373 Glioblastoma Cells

Evaluation of the Potential Cytotoxicity of Ruthenium Complex Ii Against U-373 Glioblastoma Cells

Facile Synthesis of Benzimidazoles via Oxidative Cyclization of Acyclic Monoterpene Aldehyde with Diamines: Studies on Antimicrobial and in Vivo Evaluation of Zebrafish

A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents

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