Titanium and Cancer Treatment Overview
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What is the primary challenge that titanocenes face for clinical applications?

  • Limited availability of raw materials
  • High production costs
  • Poor aqueous solubility and instability in water (correct)
  • Toxicity to healthy cells

    • What strategy was used by McGowan and coworkers to enhance the properties of titanocenes?

  • Eliminating the titanium component
  • Introducing radioactive isotopes
  • Synthesis of ring-substituted cationic titanocene dichloride derivatives (correct)
  • Mixing with another class of antitumor agents

    • What type of cancer showed significant cytotoxic activity against the improved titanocenes?

  • Lung cancer
  • Breast cancer
  • Prostate cancer
  • Cisplatin-resistant ovarian cancer (correct)

    • How do substituted fulvenes contribute to the synthesis of titanocenes?

    <p>They allow for the introduction of functional groups into titanocenes.</p> Signup and view all the answers

    What structural feature characterizes ansa-titanocenes?

    <p>A carbon–carbon bridge between Cp rings</p> Signup and view all the answers

    What process leads to the formation of ansa-titanocenes from substituted fulvenes?

    <p>Reductive dimerisation</p> Signup and view all the answers

    Which of the following best describes fulvenes?

    <p>Organic molecules with a five-membered ring system</p> Signup and view all the answers

    The research by Tacke and coworkers primarily focused on developing what kind of methods?

    <p>Novel synthetic methods starting from substituted fulvenes</p> Signup and view all the answers

    What is the significance of the hydroxyl group in the tamoxifen derivatives?

    <p>It improves recognition by the oestrogen receptor.</p> Signup and view all the answers

    Which derivative showed a higher cytotoxic effect against the MCF-7 cell line?

    <p>Tamoxifen with R = OH at 4 μM.</p> Signup and view all the answers

    Why is the vectorization of DACH–Pt considered not beneficial as an SERM?

    <p>There is no significant improvement over oxaliplatin.</p> Signup and view all the answers

    What was the unexpected result from the cytotoxicity tests of the titanocene-tamoxifen derivative?

    <p>It showed a proliferative effect.</p> Signup and view all the answers

    What is the primary challenge associated with metal-based drugs like ferrocifen?

    <p>Difficulty in finding suitable formulations.</p> Signup and view all the answers

    What is the observed RBA value of the titanocene-tamoxifen derivative?

    <p>8.5%</p> Signup and view all the answers

    Which formulation method was NOT mentioned as being researched for drug delivery of ferrocifen?

    <p>Microsphere technology.</p> Signup and view all the answers

    What effect did the titanium moiety have on the titanocene-tamoxifen derivative?

    <p>It enhanced the estrogenic effect.</p> Signup and view all the answers

    What were substituted vanadocene dichlorides found to be when tested against renal cell cancer?

    <p>Highly toxic compounds</p> Signup and view all the answers

    Which vanadium compound was evaluated as a potential treatment for Diabetes Mellitus?

    <p>Sodium vanadate</p> Signup and view all the answers

    What was the main observed effect of sodium vanadate in patients with Diabetes Mellitus?

    <p>Mild effects</p> Signup and view all the answers

    What type of studies are still needed for substituted vanadocenes after in vitro testing?

    <p>Preclinical studies</p> Signup and view all the answers

    Which of the following statements is true regarding the toxicity of substituted vanadocenes compared to titanocene?

    <p>Substituted vanadocenes are more potent and toxic than titanocene</p> Signup and view all the answers

    When were inorganic vanadium compounds evaluated for their potential treatment of Diabetes Mellitus?

    <p>End of the nineteenth century</p> Signup and view all the answers

    What is a possible clinical application of substituted vanadocenes, based on the information provided?

    <p>Treatment of renal cell cancer</p> Signup and view all the answers

    What does the compound sodium vanadate specifically target in patients with Diabetes Mellitus?

    <p>Glucose levels in the blood</p> Signup and view all the answers

    What is a significant challenge in analyzing active vanadium compounds?

    <p>Their paramagnetic character</p> Signup and view all the answers

    Which vanadium compound is noted for undergoing fast hydrolysis?

    <p>Vanadocene dichloride</p> Signup and view all the answers

    What type of vanadium complexes were found to have cytotoxic activity against testicular cancer?

    <p>Organometallic vanadium(+IV) complexes</p> Signup and view all the answers

    What did in vitro studies reveal about the substituted vanadocene compounds?

    <p>They exhibit variable cytotoxic activity.</p> Signup and view all the answers

    How does the mode of action of vanadium-induced cytotoxicity differ from that of titanocene dichloride?

    <p>It is not well understood and requires further study.</p> Signup and view all the answers

    What is a feature of the substituted vanadocene compounds being researched?

    <p>They contain substituted cyclopentadienyl ligands.</p> Signup and view all the answers

    Which compound showed no cytotoxic effect in the studies conducted?

    <p>Vanadyl(IV) sulfate</p> Signup and view all the answers

    What kind of research is being conducted alongside vanadocene analogues?

    <p>Synthesis of substituted titanocene dichlorides.</p> Signup and view all the answers

    What type of reaction allows access to benzyl-bridged titanocenes?

    <p>Hydridolithiation reaction</p> Signup and view all the answers

    Which titanocene has been reported as the most intensively studied in relation to anticancer activity?

    <p>Titanocene Y</p> Signup and view all the answers

    What is a potential disadvantage of using carbolithiation to obtain titanocenes?

    <p>It introduces additional stereocentres.</p> Signup and view all the answers

    What compound is utilized during the hydridolithiation reaction for creating titanocenes?

    <p>Superhydride (LiBEt3 H)</p> Signup and view all the answers

    What characteristic is shared by the titanocenes synthesized through hydridolithiation and carbolithiation?

    <p>Both exhibit moderate cytotoxic activity.</p> Signup and view all the answers

    What is one advantage of incorporating functional groups into titanocenes?

    <p>It improves water solubility.</p> Signup and view all the answers

    What type of cancer was specifically mentioned in the studies relating to titanocene activity?

    <p>Renal cell cancer</p> Signup and view all the answers

    How does substituent variation in titanocenes generally affect their properties?

    <p>It potentially alters their solubility.</p> Signup and view all the answers

    What is the primary purpose of the transmetallation step in the synthesis of substituted titanocenes?

    <p>To introduce titanium into the compound.</p> Signup and view all the answers

    What property did titanocenes demonstrate in in vitro experiments?

    <p>Moderate cytotoxic activity</p> Signup and view all the answers

    What was identified as the dose-limiting side effect of the treatment?

    <p>Cardiac arrhythmia</p> Signup and view all the answers

    What were the main issues faced during the clinical trials of the titanium-based compounds?

    <p>Poor water solubility and fast hydrolysis</p> Signup and view all the answers

    Which of the following compounds is associated with the synthesis described?

    <p>[Ti(bzac)2 (OEt)2]</p> Signup and view all the answers

    What aspect of the formulation led to the discontinuation of clinical trials?

    <p>The existence of isomers</p> Signup and view all the answers

    Which isomer of budotitane is classified as trans,trans,trans-?

    <p>trans,trans,trans-[Ti(bzac)2(OEt)2]</p> Signup and view all the answers

    What is the main characteristic of titanocene or titanium-based compounds that limits their effectiveness as anticancer agents?

    <p>Poor water solubility and fast hydrolysis</p> Signup and view all the answers

    What chemical reaction is represented in the synthesis of budotitane?

    <p>Ligand substitution reaction</p> Signup and view all the answers

    What is a potential consequence of the fast hydrolysis of titanium-based compounds?

    <p>Reduced therapeutic efficacy</p> Signup and view all the answers

    Study Notes

    4-Hydroxytamoxifen and Ferrocifen

    • 4-hydroxytamoxifen and ferrocifen are derivatives used in cancer treatment.
    • 4-hydroxytamoxifen showed cytotoxic effect of 6.3 µM on MCF-7 breast cancer cells.
    • Tamoxifen-vectorized derivatives also showed anti-proliferative effect.
    • The hydroxyl group in the active metabolite of tamoxifen is important in oestrogen receptor recognition.
    • Titanocene-tamoxifen derivative has an estrogenic effect comparable to that of oestrogen.
    • Proliferative effect observed with the titanocene-tamoxifen derivative.

    Titanocenes

    • Titanium (Ti) is a group 4 d-block metal.
    • It has no known native role in the human body, despite its high abundance in the earth's crust.
    • Titanium complexes are known for catalytic properties and interactions with biomolecules.
    • Titanium dioxide (TiO2) is a white solid with low aqueous solubility, used as a white pigment.
    • Research into titanium complexes as anticancer agents focuses on complexes containing functional groups that can interact with biomolecules.
    • Pharmaceutical approaches include nanoparticles, cyclodextrins, and lipid nanocapsules.

    History of Titanium-Based Anticancer Agents

    • The success of cisplatin led to research into metal-based anticancer drugs.
    • Titanocene dichloride (Cp2TiCl2) and budotitane were identified as promising drug candidates.
    • Both compounds contain labile groups analogous to cisplatin.
    • Hydrolysis in titanium compounds is faster than in cisplatin, leading to formation of hydroxo-bridges and insoluble TiO2.
    • Cp2TiCl2 is red crystalline solid with Ti(IV) center coordinated by two n-Cp ligands and two chlorine ligands.
    • The planar cyclopentadienyl ligands are coordinated to the titanium center in a bent sandwich configuration.
    • Cp2TiCl2 has only 16 VEs: six electrons from each Cp ligand, two from each Cl.
    • Titanium will accumulate near phosphorus-rich areas, indicating a titanium-DNA interaction.
    • Crystallographic studies suggest that Cp groups sterically prevent DNA cross-linking in Cp2TiCl2.
    • In cells, Ti(IV) may bind DNA backbone, which is not very strong.
    • Preclinical tests showed promising results.
    • Hydrolytic instability (loss of chlorides at low pH) is a significant challenge for clinical use.
    • Formulation as lyophilised powder or water-soluble powder is required for clinical trials.

    Vanadium Compounds (Vanadocenes)

    • Vanadium is a Group 5 d-block metal.
    • Vanadium compounds are also researched for anticancer properties.
    • Vanadium compounds are very similar in their properties to titanium.
    • Vanadium(IV) complexes exist as octahedral, tetrahedral, and diatomic oxovanadium ions.
    • Some vanadium compounds are toxic.
    • Vanadocene dichloride is structurally similar to Cp2TiCl2, but is even more prone to hydrolysis.
    • The compounds have shown some cytotoxic activity, especially against testicular cancer.
    • Vanadium compounds have exhibited potential as insulin mimetics.

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    Description

    Explore the roles of 4-hydroxytamoxifen and ferrocifen in cancer treatment, focusing on their cytotoxic effects on MCF-7 breast cancer cells. Additionally, learn about the properties of titanocene complexes and their potential as anticancer agents. This quiz provides insights into the intersection of chemistry and oncology.

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