Evaluating Ligand Modifications of the Titanocene and Auranofin Moieties for the Development of More Potent Anticancer Drugs

Fernández-Vega, Lauren; Silva, Valeria A. Ruiz; Domínguez-González, Tania M.; Claudio-Betancourt, Sebastián; Toro-Maldonado, Rafael E.; Maso, Luisa C. Capre; Ortiz, Karina Sanabria; Pérez-Verdejo, Jean A.; González, Janeishly Román; Rosado-Fraticelli, Grecia T.; Meléndez, Fabiola Pagán; Santiago, Fabiola M. Betancourt; Rivera-Rivera, Daniel A.; Chardón, Andrea C. Bruno; Vera, Axel O.; Tinoco, Arthur D.

doi:10.3390/inorganics8020010

Cited by 25 publications

(24 citation statements)

References 116 publications

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“…Titanium(IV) emerged as a promising anticancer agent soon after the discovery of cisplatin [126]. Two Ti(IV) compounds, titanocene dichloride (Cp 2 TiCl 2 ) and budotitane, made a rapid leap to clinical trials, a total of seven between both compounds [127][128][129][130][131], on account of exhibiting a broad spectrum of effect against different cell lines and not demonstrating cross-resistance with cisplatin.…”

Section: Stf May Facilitate the Cytotoxic/antiproliferative Properties Of Ti(iv) At High Metal Concentrationmentioning

confidence: 99%

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

et al. 2020

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Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

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Section: Stf May Facilitate the Cytotoxic/antiproliferative Properties Of Ti(iv) At High Metal Concentrationmentioning

confidence: 99%

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

et al. 2020

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“…The biofriendly Ti IV complexes are an attractive alternative to the toxic, Pt‐based chemotherapy [20–27] . Although early derivatives based on cyclopentadienyl or diketonato ligands failed clinical trials due to hydrolytic instability and formulation difficulties, [28–32] advanced phenolato‐based cytotoxic complexes demonstrate high stability, [26,33–46] and nanoformulation in microemulsion enhances solubility and improves drug availability [47–49] .…”

Section: Methodsmentioning

confidence: 99%

Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

et al. 2020

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Orally administered anticancer drugs facilitate treatment, but the acidic conditions in the stomach often challenge their availability. PhenolaTi is a TiIV‐based nontoxic anticancer drug with marked in‐vivo efficacy. We report that nanoformulation protects phenolaTi from decomposition in stomach‐like conditions. This is evidenced by similar NMR characteristics and similar in‐vitro cytotoxicity toward murine (CT‐26) and human (HT‐29) colon cancer cells before and after incubation of nanoformulated phenolaTi (phenolaTi‐F) at pH 2, unlike results with the unformulated form of the complex. Furthermore, administration of phenolaTi‐F in animal drinking water revealed a notable inhibition of tumor growth in Balb/c and immune‐deficient (Nude) mice inoculated with CT‐26 and HT‐29 cells, respectively. In‐vivo efficacy was at least similar to that of the corresponding intraperitoneal treatment with phenolaTi‐F and the clinically employed oral drug, capecitabine. No body weight loss or clinical signs of toxicity were evident in the phenolaTi‐F‐treated animals. These findings demonstrate a new convenient mode of cancer treatment through oral administration by safe titanium‐based drugs.

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“…Titanium(IV) emerged as a promising anticancer agent soon after the discovery of cisplatin [125]. Two Ti(IV) compounds, titanocene dichloride (Cp2TiCl2) and budotitane, made a rapid leap to clinical trials, a total of seven between both compounds [126][127][128][129][130], on account of exhibiting a broad spectrum of effect against different cell lines and not demonstrating cross-resistance with cisplatin.…”

Section: Stf May Facilitate the Cytotoxic/antiproliferative Propertiementioning

confidence: 99%

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Benjamín-Rivera¹,

Cardona-Rivera²,

Vázquez-Maldonado³

et al. 2020

Preprint

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Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.

show abstract

Evaluating Ligand Modifications of the Titanocene and Auranofin Moieties for the Development of More Potent Anticancer Drugs

Cited by 25 publications

References 116 publications

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Effective Oral Administration of an Antitumorigenic Nanoformulated Titanium Complex

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

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