scholarly journals Reactions with Proteins of Three Novel Anticancer Platinum(II) Complexes Bearing N-Heterocyclic Ligands

2021 ◽  
Vol 22 (19) ◽  
pp. 10551
Author(s):  
Francesca Sacco ◽  
Matteo Tarchi ◽  
Giarita Ferraro ◽  
Antonello Merlino ◽  
Giorgio Facchetti ◽  
...  
Keyword(s):  
Rnase A ◽  
Heterocyclic Ligands ◽  
Interacting Protein ◽  
Horse Heart Cytochrome ◽  
Anticancer Properties ◽  
Egg White Lysozyme ◽  
Pt Complex ◽  
Cyt C ◽  
Horse Heart Cytochrome C

Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.

scholarly journals Specific reduction of carboxyl groups in peptides and proteins by diborane

1969 ◽  
Vol 111 (4) ◽  
pp. 593-601 ◽  
Author(s):  
M. Z. Atassi ◽  
Arthur F. Rosenthal
Keyword(s):  
Cyclic Peptides ◽  
Acid Amide ◽  
Sperm Whale ◽  
Biological Properties ◽  
Carboxyl Groups ◽  
Peptide Bonds ◽  
Human Haemoglobin ◽  
Horse Heart Cytochrome ◽  
Egg White Lysozyme ◽  
Horse Heart Cytochrome C

1. The reaction of several peptides and proteins with diborane was studied under different conditions to determine those most suitable for the specific reduction of carboxyl groups. 2. In the reaction of model peptides and the cyclic peptides bacitracin and tyrocidin, reduction at 0° was entirely specific for the carboxyl groups without affecting the peptide bonds. Acid amide residues were not reduced. Some tripeptides showed anomalous results in that the C-terminal residue was quite resistant to reduction. 3. Specific reduction of carboxyl groups was achieved in each of the following proteins: human serum albumin, egg albumin, adult human haemoglobin, sperm-whale apomyoglobin, horse heart cytochrome c and egg-white lysozyme. The C-terminal amino acid was usually reduced. 4. Conditions for specific reduction of all available carboxyl groups are not easily found and may vary from one substance to another. Specific reduction of a limited number of available carboxyl groups may be generally accomplished by reactions at −10°. 5. It is suggested that this chemical modification, which has the advantage of permanence, may be useful in studying the role of carboxyl groups in the conformation of proteins and in the biological properties of peptides and proteins.

Kinetics and mechanism of the cytochrome c – sulfite reaction

1991 ◽  
Vol 56 (7) ◽  
pp. 1552-1559
Author(s):  
Joaquin F. Perez-Benito ◽  
Conchita Arias
Keyword(s):  
Activation Energy ◽  
Aqueous Solution ◽  
Cytochrome C ◽  
Apparent Activation Energy ◽  
Sodium Sulfite ◽  
Horse Heart Cytochrome ◽  
First Order ◽  
Cyt C ◽  
Ph Range ◽  
Horse Heart Cytochrome C

The reaction between the oxidized form of horse-heart cytochrome c and sodium sulfite in aqueous solution has been studied in the pH range 6.5 – 8.2. The reaction is first order in both oxidant and reductant, is accelerated by an increase in pH and is slowed down by addition of potassium chloride. An increase in pH results in an increase in the apparent activation energy (66-77kJ . mol-1). A mechanism in which both HSO3- and SO32- act as reducing agents is proposed, the activation energies corresponding to the cyt c-HSO3- and cyt c-SO32- reactions being 63 ± 4 and 79 ± 2 kJ mol-1, respectively.

Reactions of metallodrugs with proteins: selective binding of phosphane-based platinum(ii) dichlorides to horse heart cytochrome c probed by ESI MS coupled to enzymatic cleavage

Metallomics ◽  
2011 ◽  
Vol 3 (10) ◽  
pp. 987-990 ◽  
Author(s):  
Carolin Mügge ◽  
Elena Micheucci ◽  
Francesca Boscaro ◽  
Chiara Gabbiani ◽  
Luigi Messori ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Adduct Formation ◽  
Enzymatic Cleavage ◽  
Selective Binding ◽  
Horse Heart Cytochrome ◽  
Esi Ms ◽  
Cyt C ◽  
Horse Heart Cytochrome C

The reaction of two cis-diphosphane platinum(ii) dichlorides with horse heart cytochrome c (cyt c) leads to remarkable selectivity in terms of adduct formation.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis

2020 ◽  
Vol 17 (5) ◽  
pp. 616-618
Author(s):  
Kimia Kazemi ◽  
Negin Mozafari ◽  
Hajar Ashrafi ◽  
Pedram Rafiei ◽  
Amir Azadi
Keyword(s):  
Cell Proliferation ◽  
Mevalonate Pathway ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Interacting Protein ◽  
Akt Phosphorylation ◽  
Anticancer Properties ◽  
Proliferation And Apoptosis ◽  
Cellular Signaling Pathway ◽  
Hodgkin's Lymphomas

Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

Kinetics and mechanism of the reaction between oxidized cytochrome c and ascorbic acid

1991 ◽  
Vol 56 (2) ◽  
pp. 478-490 ◽  
Author(s):  
Joaquin F. Perez-Benito ◽  
Conchita Arias
Keyword(s):  
Ascorbic Acid ◽  
Cytochrome C ◽  
Redox Reactions ◽  
Arrhenius Equation ◽  
Horse Heart Cytochrome ◽  
First Order ◽  
Acidic Form ◽  
Ph Range ◽  
Horse Heart Cytochrome C ◽  
Mechanism Of The Reaction

The reaction between horse-heart cytochrome c and ascorbic acid has been investigated in the pH range 5.5 – 7.1 and at 10.0 – 25.0 °C. The rate shows a first-order dependence on the concentration of cytochrome c, it increases in a non-linear way as the concentration of ascorbic acid increases, it increases markedly with increasing pH and, provided that the ionic strength of the medium is high enough, it fulfills the Arrhenius equation. The apparent activation energy increases as the pH of the solution increases. The results have been explained by means of a mechanism that includes the existence of an equilibrium between two forms (acidic and basic) of oxidized cytochrome c: cyt-H+ -Fe3+ + OH- cyt -Fe3+ + H2O, whose equilibrium constant is (6.7 ± 1.4). 108 at 25.0 °C, the acidic form being more reducible than the basic one. It is suggested that there is a linkage of hydrogenascorbate ion to both forms of cytochrome c previous to the redox reactions. Two possibilities for the oxidant-reductant linkage (binding and adsorption) are discussed in detail.

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