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Role of copper chelating agents: between old applications and new perspectives in neuroscience

Neural Regeneration Research 2025年第3期20卷 751-762页

作者： Rosalba Leuci Leonardo Brunetti Vincenzo Tufarelli Marco Cerini Marco Paparella Nikola Puvača Luca Piemontese Department of Pharmacy-Pharmaceutical Science University of Bari Aldo MoroBariItaly Department of Precision and Regenerative Medicine and Jonian Area(DiMePRe-J) Section of Veterinary Science and Animal ProductionUniversity of Bari Aldo MoroBariItaly Department of Engineering Management in Biotechnology Faculty of Economics and Engineering Management in Novi SadUniversity Business Academy in Novi SadNovi SadSerbia

The role of copper element has been an increasingly relevant topic in recent years in the fields of human and animal health, for both the study of new drugs and innovative food and feed supplements. This metal plays an important role in the central nervous system, where it is associated with glutamatergic signaling, and it is widely involved in inflammatory processes. Thus, diseases involving copper(Ⅱ) dyshomeostasis often have neurological symptoms, as exemplified by Alzheimer's and other diseases(such as Parkinson's and Wilson's diseases). Moreover, imbalanced copper ion concentrations have also been associated with diabetes and certain types of cancer, including glioma. In this paper, we propose a comprehensive overview of recent results that show the importance of these metal ions in several pathologies, mainly Alzheimer's disease, through the lens of the development and use of copper chelators as research compounds and potential therapeutics if included in multi-target hybrid drugs. Seeing how copper homeostasis is important for the well-being of animals as well as humans, we shortly describe the state of the art regarding the effects of copper and its chelators in agriculture, livestock rearing, and aquaculture, as ingredients for the formulation of feed supplements as well as to prevent the effects of pollution on animal productions.

关键词： agriculture Alzheimer's disease chelators copper feed supplements multi-target

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chelators to assist the high dispersion of Ni_(2)P particles over mesoporous silica nanospheres for hydrogenating reaction

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Petroleum Science 2023年第3期20卷 1895-1902页

作者： Di Hu En-Hua Wang Ao-Cheng Wang Ai-Jun Duan State Key Laboratory of Heavy Oil Processing China University of Petroleum-BeijingBeijing102249China

NizP supported catalysts exhibit high catalytic activities in hydrogenation reaction,of which the particle sizes of Ni_(2)P active phases are the key influential factor.This research focus on the effect of chelators on the size of Ni_(2)P particles over wrinkle silica nanoparticles(WSNs)by introducing chelating agents EDTA and NTA during impregnation process.The characterization results show that chelators modified cata-lysts possess smaller size of Ni_(2)P particles than the unmodified Ni_(2)P catalysts.Among all the synthesized catalysts,the EDTA modified Ni_(2)PE(1.5)/WSNs catalyst possesses smallest average particle size of Ni_(2)P,only 2.6 nm.Moreover,the Ni_(2)P catalysts with the assistance of EDTA exhibits better catalytic activity than that of NTA under high reaction temperature,which can be ascribed to the strong bonding between EDTA and Ni.And the EDTA modified Ni_(2)PE(1.5)/WSNs catalyst shows highest hydrogenation ability,almost reaching 100%decalin selectivity.

关键词： Wrinkle silica nanoparticles chelators Ni_(2)P supported catalysts Naphthalene hydrogenation

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Neutralising effects of small molecule toxin inhibitors on nanofractionated coagulopathic Crotalinae snake venoms

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Acta Pharmaceutica Sinica B 2020年第10期10卷 1835-1845页

作者： Chunfang Xie Julien Slagboom Laura-Oana Albulescu Govert W.Somsen Freek J.Vonk Nicholas R.Casewell Jeroen Kool Amsterdam Institute of Molecular and Life Sciences Division of BioAnalytical ChemistryDepartment of Chemistry and Pharmaceutical SciencesFaculty of ScienceVrije Universiteit AmsterdamAmsterdam 1081HVThe Netherlands Centre for Analytical Sciences Amsterdam(CASA) Amsterdam 1098 XHThe Netherlands Centre for Snakebite Research and Interventions Liverpool School of Tropical MedicineLiverpool L35QAUK Centre for Drugs and Diagnostics Liverpool School of Tropical MedicineLiverpool L35QAUK Naturalis Biodiversity Center Leiden 2333 CRThe Netherlands

Repurposing small molecule drugs and drug candidates is considered as a promising approach to revolutionise the treatment of snakebite envenoming.In this study,we investigated the inhibiting effects of the small molecules varespladib(nonspecific phospholipase A2 inhibitor),marimastat(broad spectrum matrix metalloprotease inhibitor)and dimercaprol(metal ion chelator)against coagulopathic toxins found in Crotalinae(pit vipers)snake venoms.Venoms from Bothrops asper,Bothrops jararaca,Calloselasma rhodostoma and Deinagkistrodon acutus were separated by liquid chromatography,followed by nanofractionation and mass spectrometry identification undertaken in parallel.Nanofractions of the venom toxins were then subjected to a high-throughput coagulation assay in the presence of different concentrations of the small molecules under study.Anticoagulant venom toxins were mostly identified as phospholipases A2,while procoagulant venom activities were mainly associated with snake venom metalloproteinases and snake venom serine proteases.Varespladib was found to effectively inhibit most anticoagulant venom effects,and also showed some inhibition against procoagulant toxins.Contrastingly,marimastat and dimercaprol were both effective inhibitors of procoagulant venom activities but showed little inhibitory capability against anticoagulant toxins.The information obtained from this study aids our understanding of the mechanisms of action of toxin inhibitor drug candidates,and highlights their potential as future snakebite treatments.

关键词： Snakebite Antivenom Varespladib Marimastat Dimercaprol chelators Nanofractionation

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Synthesis of a Novel Chiral Trihydroxamic Acid Containing L-Pro-L-Ala-L-Ala-β-(HO)Ala-OMe Unit

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Chinese Chemical Letters 2006年第6期17卷 751-754页

作者： Lang Tao SHEN Ting YANG Hong Yu LI Zhi Fu LUO National lsotope Center of Engineering and Technology China Institute of Atomic EnergyBeijing P. O. Box 275 （58） Beijing 102413 Medical Isotope Research Center Peking University Beijing 100083

An N-hydroxyl peptide unit of H-L-Pro-L-Ala-L-Ala-β-（BnO）Ala-OMe was synthesized by stepwise chain building method in solution. Then, based on nitrilotriacetic acid backbone and this N-hydroxyl peptide unit, a novel chiral tripodal ligand P as an analogue of desferrichrome, has been synthesized. In neutral pH, ligand P formed stable tri（hydroxamato）- iron（Ⅲ） complexes which showed a maximum absorptiota （∑max=2750 M^-lcm^-1） at 422 nm in UV-Vis spectra. The characteristic absorption spectra are similar to those of natural trihydroxamate-type siderophores.

关键词： Hydroxamic acid siderophores tripodal ligand chelators iron.

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Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function

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World Journal of Gastroenterology 2016年第32期22卷 7252-7263页

作者： Taro Takami Takahiro Yamasaki Issei Saeki Toshihiko Matsumoto Yutaka Suehiro Isao Sakaida Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of Medicine

Hepatocellular carcinoma(HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids(BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis.

关键词： Hepatocellular carcinoma Liver cirrhosis Branched-chain amino acids Late evening snack Iron chelators Bone marrow cells

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