scholarly journals Molecular and Cellular Mechanisms of Cytotoxic Activity of Vanadium Compounds against Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1757 ◽  
Author(s):  
Szymon Kowalski ◽  
Dariusz Wyrzykowski ◽  
Iwona Inkielewicz-Stępniak
Keyword(s):  
Cytotoxic Activity ◽  
Metal Ion ◽  
Vanadium Complexes ◽  
Metal Ion Binding ◽  
Cellular Mechanisms ◽  
Design And Synthesis ◽  
New Perspective ◽  
Living Organisms ◽  
And Function ◽  
Programed Cell Death

Discovering that metals are essential for the structure and function of biomolecules has given a completely new perspective on the role of metal ions in living organisms. Nowadays, the design and synthesis of new metal-based compounds, as well as metal ion binding components, for the treatment of human diseases is one of the main aims of bioinorganic chemistry. One of the areas in vanadium-based compound research is their potential anticancer activity. In this review, we summarize recent molecular and cellular mechanisms in the cytotoxic activity of many different synthetic vanadium complexes as well as inorganic salts. Such mechanisms shall include DNA binding, oxidative stress, cell cycle regulation and programed cell death. We focus mainly on cellular studies involving many type of cancer cell lines trying to highlight some new significant advances.

scholarly journals Ferrochelatase: the convergence of the porphyrin biosynthesis and iron transport pathways

2011 ◽  
Vol 15 (05n06) ◽  
pp. 350-356 ◽  
Author(s):  
Gregory A. Hunter ◽  
Salam Al-Karadaghi ◽  
Gloria C. Ferreira
Keyword(s):  
Active Site ◽  
Ferrous Iron ◽  
Metal Ion ◽  
Iron Transport ◽  
Enzyme Commission Number ◽  
Metal Ion Binding ◽  
Active Site Residues ◽  
Transport Pathways ◽  
Living Organisms

Ferrochelatase (also known as PPIX ferrochelatase; Enzyme Commission number 4.9.9.1.1) catalyzes the insertion of ferrous iron into PPIX to form heme. This reaction unites the biochemically synchronized pathways of porphyrin synthesis and iron transport in nearly all living organisms. The ferrochelatases are an evolutionarily diverse family of enzymes with no more than six active site residues known to be perfectly conserved. The availability of over thirty different crystal structures, including many with bound metal ions or porphyrins, has added tremendously to our understanding of ferrochelatase structure and function. It is generally believed that ferrous iron is directly channeled to ferrochelatase in vivo, but the identity of the suspected chaperone remains uncertain despite much recent progress in this area. Identification of a conserved metal ion binding site at the base of the active site cleft may be an important clue as to how ferrochelatases acquire iron, and catalyze desolvation during transport to the catalytic site to complete heme synthesis.

scholarly journals The Advantages of EPR Spectroscopy in Exploring Diamagnetic Metal Ion Binding and Transfer Mechanisms in Biological Systems

2021 ◽  
Vol 8 (1) ◽  
pp. 3
Author(s):  
Shelly Meron ◽  
Yulia Shenberger ◽  
Sharon Ruthstein
Keyword(s):  
Ligand Binding ◽  
Conformational Changes ◽  
Epr Spectroscopy ◽  
Metal Ion ◽  
Copper Ion ◽  
Biological Processes ◽  
Ion Transfer ◽  
Metal Ion Binding ◽  
Cellular Mechanisms ◽  
Paramagnetic Resonance

Electron paramagnetic resonance (EPR) spectroscopy has emerged as an ideal biophysical tool to study complex biological processes. EPR spectroscopy can follow minor conformational changes in various proteins as a function of ligand or protein binding or interactions with high resolution and sensitivity. Resolving cellular mechanisms, involving small ligand binding or metal ion transfer, is not trivial and cannot be studied using conventional biophysical tools. In recent years, our group has been using EPR spectroscopy to study the mechanism underlying copper ion transfer in eukaryotic and prokaryotic systems. This mini-review focuses on our achievements following copper metal coordination in the diamagnetic oxidation state, Cu(I), between biomolecules. We discuss the conformational changes induced in proteins upon Cu(I) binding, as well as the conformational changes induced in two proteins involved in Cu(I) transfer. We also consider how EPR spectroscopy, together with other biophysical and computational tools, can identify the Cu(I)-binding sites. This work describes the advantages of EPR spectroscopy for studying biological processes that involve small ligand binding and transfer between intracellular proteins.

scholarly journals The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Débora Bifano Pimenta ◽  
Vanessa Araujo Varela ◽  
Tarcila Santos Datoguia ◽  
Victória Bulcão Caraciolo ◽  
Gabriel Herculano Lopes ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Microenvironment ◽  
Cellular Mechanisms ◽  
Cytokines And Chemokines ◽  
New Perspective ◽  
Basic Studies ◽  
And Function ◽  
Acute Myeloid

Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that mediate important functions on hematopoietic cells and leukemic blasts. There are some evidences of how AML modify the architecture and function of these three BM niches, but it has been still unclear how essential those modifications are to maintain AML development. Basic studies and clinical trials have been suggesting that disturbing specific cells and molecules into the BM niches might be able to impair leukemia competencies. Either through niche-specific molecule inhibition alone or in combination with more traditional drugs, the bone marrow microenvironment is currently considered the potential target for new strategies to treat AML patients. This review describes the cellular and molecular constitution of the BM niches under healthy and AML conditions, presenting this anatomical compartment by a new perspective: as a prospective target for current and next generation therapies.

scholarly journals Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3610 ◽  
Author(s):  
Suresh K. Bowroju ◽  
Nirjal Mainali ◽  
Srinivas Ayyadevara ◽  
Narsimha R. Penthala ◽  
Sesha Krishnamachari ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Metal Ion ◽  
Docking Studies ◽  
Indole Derivatives ◽  
Metal Ion Binding ◽  
Hybrid Compound ◽  
Design And Synthesis ◽  
Aβ Aggregation ◽  
Self Aggregation

A series of novel hybrid 8-hydroxyquinoline-indole derivatives (7a–7e, 12a–12b and 18a–18h) were synthesized and screened for inhibitory activity against self-induced and metal-ion induced Aβ1–42 aggregation as potential treatments for Alzheimer’s disease (AD). In vitro studies identified the most inhibitory compounds against self-induced Aβ1–42 aggregation as 18c, 18d and 18f (EC50 = 1.72, 1.48 and 1.08 µM, respectively) compared to the known anti-amyloid drug, clioquinol (1, EC50 = 9.95 µM). The fluorescence of thioflavin T-stained amyloid formed by Aβ1–42 aggregation in the presence of Cu2+ or Zn2+ ions was also dramatically decreased by treatment with 18c, 18d and 18f. The most potent hybrid compound 18f afforded 82.3% and 88.3% inhibition, respectively, against Cu2+- induced and Zn2+- induced Aβ1–42 aggregation. Compounds 18c, 18d and 18f were shown to be effective in reducing protein aggregation in HEK-tau and SY5Y-APPSw cells. Molecular docking studies with the most active compounds performed against Aβ1–42 peptide indicated that the potent inhibitory activity of 18d and 18f were predicted to be due to hydrogen bonding interactions, π–π stacking interactions and π–cation interactions with Aβ1–42, which may inhibit both self-aggregation as well as metal ion binding to Aβ1–42 to favor the inhibition of Aβ1–42 aggregation.

Photophysical Characterisation, Metal Ion Binding and Enantiomeric Recognition of Chiral Ligands Containing Phenazine Fluorophore

2004 ◽  
Vol 69 (4) ◽  
pp. 885-896 ◽  
Author(s):  
Luisa Stella Dolci ◽  
Péter Huszthy ◽  
Erika Samu ◽  
Marco Montalti ◽  
Luca Prodi ◽  
...  
Keyword(s):  
Metal Ion ◽  
Photophysical Properties ◽  
Ion Binding ◽  
Metal Ion Binding ◽  
Ammonium Ions ◽  
Enantiomerically Pure ◽  
Binding Process ◽  
High Affinity ◽  
Enantiomeric Recognition ◽  
Chiral Species

Enantiomerically pure dimethyl- and diisobutyl-substituted phenazino-18-crown-6 ligands bind metal and ammonium ions and also primary aralkylammonium perchlorates in acetonitrile with high affinity, causing pronounced changes in their luminescence properties. In addition, they show enantioselectivity towards chiral primary aralkylammonium perchlorates. The possibility to monitor the binding process by photoluminescence spectroscopy can gain ground for the design of very efficient enantioselective chemosensors for chiral species. The observed changes in the photophysical properties are also an important tool for understanding the interactions present in the adduct.

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