Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety

Chen, Bi-Chun; Lu, Junjian; Jiang, Ning; Ma, Xiu-Rong; Li, Rong‐Tao; Ye, Rui-Rong

doi:10.1007/s00775-021-01901-8

Cited by 13 publications

(7 citation statements)

References 57 publications

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“…The interaction with Ru-IM and this cell organelle was further investigated to assess whether changes to mitochondrial function were observed with exposure to the ruthenium compound. Mitochondrial dysfunction has been reported for other ruthenium anticancer agents , and may give insight into their underlying mechanism of action. Cell Painting, a high content imaging assay, was used to ascertain the morphological profile of Ru-IM against five multiplexed dyes–actin, RNA, endoplasmic reticulum (ER), mitochondria, and nuclei, as detailed in Figure B.…”

Section: Resultsmentioning

confidence: 99%

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Nayeem,

Sauma,

Ahad

et al. 2024

ACS Pharmacol. Transl. Sci.

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Triple negative breast cancer (TNBC) represents a subtype of breast cancer that does not express the three major prognostic receptors of human epidermal growth factor receptor 2 (HER2), progesterone (PR), and estrogen (ER). This limits treatment options and results in a high rate of mortality. We have reported previously on the efficacy of a water-soluble, cationic organometallic compound (Ru-IM) in a TNBC mouse xenograft model with impressive tumor reduction and targeted tumor drug accumulation. Ru-IM inhibits cancer hallmarks such as migration, angiogenesis, and invasion in TNBC cells by a mechanism that generates apoptotic cell death. Ru-IM displays little interaction with DNA and appears to act by a P53-independent pathway. We report here on the mitochondrial alterations caused by Ru-IM treatment and detail the inhibitory properties of Ru-IM in the PI3K/AKT/mTOR pathway in MDA-MB-231 cells. Lastly, we describe the results of an efficacy study of the TNBC xenografted mouse model with Ru-IM and Olaparib monotherapy and combinatory treatments. We find 59% tumor shrinkage with Ru-IM and 65% with the combination. Histopathological analysis confirmed no test-article-related toxicity. Immunohistochemical analysis indicated an inhibition of the angiogenic marker CD31 and increased levels of apoptotic cleaved caspase 3 marker, along with a slight inhibition of p-mTOR. Taken together, the effects of Ru-IM in vitro show similar trends and translation in vivo. Our investigation underscores the therapeutic potential of Ru-IM in addressing the challenges posed by TNBC as evidenced by its robust efficacy in inhibiting key cancer hallmarks, substantial tumor reduction, and minimal systemic toxicity.

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Section: Resultsmentioning

confidence: 99%

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Nayeem,

Sauma,

Ahad

et al. 2024

ACS Pharmacol. Transl. Sci.

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“…Instead, we summarize these ruthenium complexes formed by natural ligands (Fig. 4, 5 and Table 1) due to the increasing number of studies on natural products and their derivatives as ligands for ruthenium complexes, 61,62 such as β-carboline, isoquinoline, curcumin, [63][64][65][66][67][68] amino acids, 69 flavonoids, 70,71 sugars, 72,73 etc.…”

Section: Development Of Ruthenium Complex Moleculesmentioning

confidence: 99%

Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy

Zhu

et al. 2022

Nanoscale

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“…Their structural variability allows for the design of complexes with tailored properties optimized for specific cancer types. However, rigorous research is ongoing to assess their toxicity, bio distribution, and overall safety profile in order to translate these findings into effective and safe anticancer treatments (Chen et al 2021;Awwadiet al 2022).…”

Section: Introductionmentioning

confidence: 99%

Anticancer and antiproliferative activity of ruthenium complex (II) bearing 3,3’-dicarboxy-2,2’-bipyridine ligand

Saadh

2023

PHAR

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Even though significant progress has been made in cancer treatment, there is always room for improvement. The experimental drug Ruthenium Complex II shows promise as a cancer treatment. In this article, the dichloro-3,3’-dicarboxy-2,2’-bipyridyl bis(dimethylsulphoxide)ruthenium(II) [RuCl2(3,3’-dcbpy)(DMSO)2], have been synthesized, characterized, and studied for its anticancer activity against MDA-MB-231 and MRC-5 cell lines, as well as its mechanisms of action and selectivity. According to research, [RuCl2 (3,3’-dcbpy)(DMSO)2], is highly cytotoxic to the MDA-MB-231 and minimum cytotoxic to MRC-5 cell lines, with IC50 values of 5.95 and 579.6 μg/ml, respectively. Ruthenium Complex II is exceptionally effective at destroying cancer cells while causing minimal harm to healthy cells. RuCl2(3,3’-dcbpy)(DMSO)2] caused apoptosis, which was confirmed by the activation of caspase-3. Ruthenium complexes hold great promise as powerful anticancer agents. Their unique mechanisms of action, ability to selectively target cancer cells, and versatility in chemical structure make them attractive candidates for the development of targeted therapies.

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Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety

Cited by 13 publications

References 57 publications

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Insights into Mechanisms and Promising Triple Negative Breast Cancer Therapeutic Potential for a Water-Soluble Ruthenium Compound

Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy

Anticancer and antiproliferative activity of ruthenium complex (II) bearing 3,3’-dicarboxy-2,2’-bipyridine ligand

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