Article
Chemistry, Multidisciplinary
Mahendiran Dharmasivam, Busra Kaya, Tharushi P. Wijesinghe, Vera Richardson, Jeffrey R. Harmer, Miguel A. Gonzalvez, William Lewis, Mahan Gholam Azad, Paul V. Bernhardt, Des R. Richardson
Summary: This study investigates the synthesis and characterization of metal complexes of the Dp4e4mT analog, revealing their distinct effects and off-target activities in cancer treatment, with a key role played by differential transmetallation.
Article
Biochemistry & Molecular Biology
O. Yu. Selyutina, P. A. Kononova, V. E. Koshman, E. A. Shelepova, M. Gholam Azad, R. Afroz, M. Dharmasivam, Paul V. Bernhardt, N. E. Polyakov, D. R. Richardson
Summary: Ascorbate-driven redox cycling enhances the anti-proliferative activity of Dp44mT and Emodin.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Review
Cell Biology
Yurong Zhang, Dianlun Qian, Xiangfeng Bai, Shibo Sun
Summary: Ferroptosis is a type of iron-dependent cell death caused by lipid peroxide accumulation, and it is implicated in pulmonary infectious diseases. Dysregulation of iron metabolism, accumulation of lipid peroxides, and inactivation/consumption of glutathione peroxidase 4 (GPX4) are the main contributors to ferroptosis. Infections caused by Pseudomonas aeruginosa, Mycobacterium tuberculosis, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are associated with ferroptosis. Ferroptosis may serve as a potential therapeutic target for pulmonary infectious diseases, but its involvement and relationship with Staphylococcus aureus, Klebsiella pneumoniae, and Leishmania spp infections remain unclear. Further research is needed.
CELLULAR MICROBIOLOGY
(2023)
Article
Chemistry, Medicinal
Mahendiran Dharmasivam, Busra Kaya, Tharushi Wijesinghe, Mahan Gholam Azad, Miguel A. Gonzalvez, Mohammad Hussaini, Jason Chekmarev, Paul Bernhardt, Des R. Richardson
Summary: A novel and selective antitumor agent, 3-thiosemicarbazone (PPP44mT), and its analogues with distinctive properties were synthesized and characterized. The inclusion of a styrene moiety prevented the oxidation of oxy-myoglobin or oxy-hemoglobin, which is different from other potent thiosemicarbazones such as DpC or Dp44mT. PPP44mT and its Cu(II) complexes exhibited immediate cytotoxicity against SK-N-MC tumor cells, while [Zn(PPP44mT)2] showed delayed antiproliferative efficacy and superior inhibition of cyclin D1 expression compared to DpC or Dp44mT.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Hadi Kargar, Mehdi Fallah-Mehrjardi, Muhammad Ashfaq, Khurram Shahzad Munawar, Muhammad Nawaz Tahir
Summary: A cis-dioxomolybdenum Schiff base complex has been synthesized and characterized by various spectroscopic methods. The crystal structure of the complex was determined using single crystal X-ray diffraction, revealing a distorted octahedral coordination geometry. The synthesized complex exhibits catalytic potential for the oxidation of sulfides, yielding sulfoxides and sulfones in high yields and short reaction times.
JOURNAL OF MOLECULAR STRUCTURE
(2023)
Review
Medicine, Research & Experimental
Hosam M. Habib, Sahar Ibrahim, Aamnah Zaim, Wissam H. Ibrahim
Summary: Iron overload is increasingly seen as a contributor to the pathogenesis of COVID-19, triggering inflammation, hypercoagulation, hyperferritinemia, and immune dysfunction. Iron chelators, including the naturally occurring lactoferrin, may hold therapeutic value in COVID-19 by modulating the immune response and blocking the entry of coronaviruses into host cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Hadi Darvishi-Khezri, Mohammad Naderisorki, Mohammad Zahedi, Parham Mortazavi, Fatemeh Tajik, Amirreza Nasirzadeh, Hossein Karami
Summary: The combination therapy of silymarin and iron chelators in transfusion-dependent beta-thalassemia patients can significantly improve serum ferritin levels, but does not have a significant effect on reducing liver iron concentration.
EXPERT REVIEW OF CLINICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fredson Torres Silva, Breno Pannia Esposito
Summary: This study evaluated the key properties of five candidate phytochelators for iron overload diseases and found that tropolone and mimosine showed good binding capacity for iron, as well as antioxidant activity. They were also cell permeant and able to access labile pools of iron. These results suggest the potential of these molecules, especially mimosine, as adjuvants in treatments for iron overload.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2022)
Article
Infectious Diseases
Victor Vinuesa, Raquel Cruces, Francesca Nonnoi, Michael J. McConnell
Summary: Novel synergy between LpxC inhibitors and iron chelators or gallium nitrate has been identified against A. baumannii strains, leading to a significant reduction in bacterial growth.
Article
Medicine, General & Internal
M. Ruivard, H. Lobbes
Summary: The etiological investigation of hyperferritinemia involves clinical examination and biological tests. Dysmetabolic iron overload syndrome is the most common iron overload disease, and the effectiveness of bloodletting therapy is uncertain. Type 1 genetic hemochromatosis results in iron accumulation, but phenotypic expression varies. Elastography can be used to identify hepatic fibrosis in cases of elevated ferritin levels. Chelators are used for iron overload associated with anemia, with hepatic iron content needing to be controlled. Deferoxamine is the preferred treatment for severe iron overload or emergency conditions.
REVUE DE MEDECINE INTERNE
(2023)
Review
Biochemistry & Molecular Biology
Usama Abbasi, Srinivas Abbina, Arshdeep Gill, Lily E. Takuechi, Jayachandran N. Kizhakkedathu
Summary: This article discusses the essential role of iron in the human body, the importance of iron homeostasis, and the effects of iron deficiency and excess on the body. It also explores the use of iron chelation strategies in alleviating the toxicity of excess iron.
ACS CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Anver Basha Shaik, Comfort A. Boateng, Francisco O. Battiti, Alessandro Bonifazi, Jianjing Cao, Li Chen, Rezvan Chitsazi, Saiprasad Ravi, Kuo Hao Lee, Lei Shi, Amy Hauck Newman
Summary: The crystal structure of dopamine D-3 receptor in complex with eticlopride led to the design of bitopic ligands exploring various alterations to the pyrrolidine ring, which were found to impact binding affinities with dopamine D2R/D3R. The study showed that small pyrrolidine N-alkyl groups were poorly tolerated, and O-alkylated analogues exhibited higher affinities compared to N-alkylated ones. Molecular models suggested that modifications at the 4-position could be well-tolerated for future D2R/D3R bioconjugate tools.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Physical
Katarzyna Gobis, Malgorzata Szczesio, Andrzej Olczak, Izabela Korona-Glowniak, Ewa Augustynowicz-Kopec, Ida Mazernt-Politowicz, Dagmara Ziembicka, Marek L. Glowka
Summary: In this study, four novel methyl 4-phenylpicolinoimidate derivatives of hydrazone were synthesized and evaluated for their antimicrobial activity. Compound 3b exhibited significant activity against Gram-positive bacteria, while derivatives 3a and 4a showed higher activity against tuberculosis. These findings provide valuable insights for the development of antimicrobial and anti-tuberculosis drugs.
Article
Chemistry, Inorganic & Nuclear
Cristina Gonzalez-Garcia, Cristina Garcia-Pascual, Rodrigo Buron, David G. Calatayud, Josefina Perles, M. Antonia Mendiola, Elena Lopez-Torres
Summary: In this study, a new dissymmetric bis(thiosemicarbazone) ligand was prepared and characterized. The reactivity of this ligand and the hybrid isopropylthiosemicarbazone/naphtoylhydrazone with zinc(II), copper(II), and nickel(II) nitrates was explored. The results showed that the deprotonation of the ligand could not be selectively controlled. Additionally, different supramolecular architectures were formed based on the degree of deprotonation of the ligands and the presence of nitrate ions.
Review
Chemistry, Medicinal
Gangliang Huang, Shiyu Huang
Summary: Glucan has gained attention in life science research for its various advantages, but there are still two main issues in pharmacodynamics, including a lack of information on its mechanism of action and slow progress in the study of structure-activity relationships.
PHYTOTHERAPY RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Palraj Kalimuthu, Dominik Hege, Agnieszka Winiarska, Yvonne Gemmecker, Maciej Szaleniec, Johann Heider, Paul V. Bernhardt
Summary: In contrast to molybdenum enzymes, tungsten enzymes have lower redox potentials and can perform reversible redox transformations. However, the electrochemical properties of tungsten enzymes have received less attention. In this study, the tungsten enzyme aldehyde oxidoreductase (AOR) from Aromatoleum aromaticum was immobilized on a glassy carbon electrode. The system showed electrocatalytic oxidation of aromatic and aliphatic aldehydes in the presence of electron transfer mediators. The different mediators had different electron transfer rates and methylene blue acted as a two-electron acceptor. This work demonstrates a highly energy efficient catalytic process for aldehyde oxidation at low applied electrochemical potential.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Medicinal
Mahendiran Dharmasivam, Busra Kaya, Tharushi Wijesinghe, Mahan Gholam Azad, Miguel A. Gonzalvez, Mohammad Hussaini, Jason Chekmarev, Paul Bernhardt, Des R. Richardson
Summary: A novel and selective antitumor agent, 3-thiosemicarbazone (PPP44mT), and its analogues with distinctive properties were synthesized and characterized. The inclusion of a styrene moiety prevented the oxidation of oxy-myoglobin or oxy-hemoglobin, which is different from other potent thiosemicarbazones such as DpC or Dp44mT. PPP44mT and its Cu(II) complexes exhibited immediate cytotoxicity against SK-N-MC tumor cells, while [Zn(PPP44mT)2] showed delayed antiproliferative efficacy and superior inhibition of cyclin D1 expression compared to DpC or Dp44mT.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Xiao Zhao, Des R. Richardson
Summary: Breast cancer is the leading cause of cancer death in women, and there are different clinical subtypes based on hormone receptor and HER2 status. Targeted therapies exist for ER-α positive and HER2 overexpressing tumors, but resistance and metastasis remain problems, while TNBC lacks suitable targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Chemistry, Inorganic & Nuclear
Miguel A. Gonzalvez, Craig M. Williams, Manuel Martinez, Paul V. Bernhardt
Summary: Organocopper(II) reagents are a relatively unexplored frontier in copper catalysis. This study investigates the stability and reactivity of Cu-II-C bonds, proposing two main pathways for their cleavage: homolysis and heterolysis. Experimental results provide insights into the reaction pathways of organocopper(II) complexes, which are relevant to their application as catalysts in C-C bond forming reactions.
INORGANIC CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Zhao Deng, Des R. Richardson
Summary: This review explores the interactions between Myc proteins and other molecules, focusing on the relationship between N-Myc and NDRG1 and potential therapeutic interventions. These findings provide important insights into the understanding and treatment of neuroblastoma.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Xiaoyi Chen, Yunjiang Feng, Ronald J. Quinn, Dean L. Pountney, Des R. Richardson, George D. Mellick, Linlin Ma
Summary: Parkinson's disease is a neurode-generative disorder caused by the loss of dopaminergic neurons in the midbrain, leading to motor symptoms. Understanding the biological targets and pathways involved in the disease is crucial for developing effective treatments. Ion channels, particularly potassium channels, play important roles in neuronal function and neuroinflammation, making them potential therapeutic targets. This review discusses the role of specific potassium channel subfamilies in Parkinson's disease pathogenesis and their potential as targets for neuroprotective drugs.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Chemistry, Inorganic & Nuclear
Masnun Naher, Chuyi Su, Jeffrey R. Harmer, Craig M. Williams, Paul V. Bernhardt
Summary: The utility and scope of Cu-catalyzed halogen atom transfer chemistry have been exploited in a variety of fields. This study demonstrates the ability to modulate the reactivity of the Cu catalyst using electrochemistry, resulting in unprecedented rate acceleration in Cu-catalyzed bulk electrosynthesis.
INORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Tyler Fahrenhorst-Jones, Dehui Kong, Jed M. Burns, Gregory K. Pierens, Paul V. Bernhardt, G. Paul Savage, Craig M. Williams
Summary: It is found that seco-1-Azacubane-2-carboxylic acid can undergo amide bond formation at both the N- and C-termini using proline-based bioactive molecule templates as a concept platform.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Palraj Kalimuthu, Sheron Hakopian, Dimitri Niks, Russ Hille, Paul V. Bernhardt
Summary: In this study, an electrocatalytically active formate oxidation/CO2 reduction system was developed based on FdsDABG from Cupriavidus necator, providing new insights into the kinetics of the enzyme catalytic mechanism.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Pharmacology & Pharmacy
Faten Shehadeh-Tout, Heloisa H. Milioli, Suraya Roslan, Patric J. Jansson, Mahendiran Dharmasivam, Dinny Graham, Robin Anderson, Tharushi Wijesinghe, Mahan Gholam Azad, Des R. Richardson, Zaklina Kovacevic
Summary: This study investigates a new class of anti-cancer agents for the treatment of ER-positive breast cancer. These agents inhibit multiple growth factor receptors and down-stream signaling, leading to decreased expression of hormone receptors and key resistance pathways. In vivo experiments demonstrate that these agents effectively inhibit ER-positive breast cancer growth. This represents an innovative non-hormonal, multi-modal therapeutic approach.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Tyler Fahrenhorst-Jones, David L. Marshall, Jed. M. Burns, Gregory K. Pierens, Robert E. Hormann, Allison M. Fisher, Paul V. Bernhardt, Stephen J. Blanksby, G. Paul Savage, Philip E. Eaton, Craig M. Williams
Summary: Highly strained cage hydrocarbons have been widely used to explore chemical stability and reactivity, probe physical properties, and as bioactive molecules and in materials discovery. However, the nitrogenous congeners have received less attention. This study presents the synthesis of 1-azahomocubane and its comprehensive characterization, physical property analysis, and chemical reactivity investigation. The findings suggest that nitrogen is well tolerated in a highly strained environment.
Article
Chemistry, Multidisciplinary
Mahendiran Dharmasivam, Busra Kaya, Tharushi P. Wijesinghe, Vera Richardson, Jeffrey R. Harmer, Miguel A. Gonzalvez, William Lewis, Mahan Gholam Azad, Paul V. Bernhardt, Des R. Richardson
Summary: This study investigates the synthesis and characterization of metal complexes of the Dp4e4mT analog, revealing their distinct effects and off-target activities in cancer treatment, with a key role played by differential transmetallation.
Article
Chemistry, Multidisciplinary
Jeffrey R. Harmer, Sheron Hakopian, Dimitri Niks, Russ Hille, Paul V. Bernhardt
Summary: This article investigates the redox properties of an oxygen-tolerant and molybdenum-dependent formate dehydrogenase, providing insights into the highly efficient catalytic activity of formate oxidation and CO2 reduction associated with the enzyme.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Paul V. Bernhardt
Summary: The accurate measurement of protein redox potentials is an important task. Traditional methods have significant experimental errors. This paper proposes an automated approach that combines continuous scanning potential with time-resolved UV-vis spectroscopy, allowing for fast and accurate measurement of protein redox potentials.