Frontiers of metal-coordinating drug design

Palermo, Giulia; Spinello, Angelo; Saha, Aakash; Magistrato, Alessandra

doi:10.1080/17460441.2021.1851188

Cited by 31 publications

(20 citation statements)

References 158 publications

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“…In addition, zinc deficiency can cause immune dysfunction, which can enhance the inflammatory effects of interleukin, inhibit the effects of interleukin on lymphocytes, and promote apoptosis, angiogenesis, and metastasis. Zinc is often involved in gene expression, the maintenance of protein and nucleic acid structure, intracellular molecular transport, and immune functions performed by zinc-finger proteins ( 43 – 45 ). Studies have shown that zinc lipoprotein is involved in cancer-related biological processes, can inhibit the proliferation and invasion of cancer cells, and has a protective effect on the occurrence of prostate cancer ( 46 – 48 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Multi-Omics Analysis Model to Identify Biomarkers Associated With Prognosis of Breast Cancer

Fan

Kao

et al. 2022

Front. Oncol.

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BackgroundWith the rapid development and wide application of high-throughput sequencing technology, biomedical research has entered the era of large-scale omics data. We aim to identify genes associated with breast cancer prognosis by integrating multi-omics data.MethodGene-gene interactions were taken into account, and we applied two differential network methods JDINAC and LGCDG to identify differential genes. The patients were divided into case and control groups according to their survival time. The TCGA and METABRIC database were used as the training and validation set respectively.ResultIn the TCGA dataset, C11orf1, OLA1, RPL31, SPDL1 and IL33 were identified to be associated with prognosis of breast cancer. In the METABRIC database, ZNF273, ZBTB37, TRIM52, TSGA10, ZNF727, TRAF2, TSPAN17, USP28 and ZNF519 were identified as hub genes. In addition, RPL31, TMEM163 and ZNF273 were screened out in both datasets. GO enrichment analysis shows that most of these hub genes were involved in zinc ion binding.ConclusionIn this study, a total of 15 hub genes associated with long-term survival of breast cancer were identified, which can promote understanding of the molecular mechanism of breast cancer and provide new insight into clinical research and treatment.

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Section: Discussionmentioning

confidence: 99%

Integrated Multi-Omics Analysis Model to Identify Biomarkers Associated With Prognosis of Breast Cancer

Fan

Kao

et al. 2022

Front. Oncol.

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“…The design of iron-and copper-chelating agents was initially based on relatively simple structures of complexing agents [7][8][9][10]. Essentially, principles of classical coordination chemistry, which goes back to Alfred Werner, have been used for this purpose [11].…”

Section: Coordination Chemistry Of Iron and Coppermentioning

confidence: 99%

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

et al. 2021

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Iron and copper are essential micronutrients needed for the proper function of every cell. However, in excessive amounts, these elements are toxic, as they may cause oxidative stress, resulting in damage to the liver and other organs. This may happen due to poisoning, as a side effect of thalassemia infusion therapy or due to hereditary diseases hemochromatosis or Wilson’s disease. The current golden standard of therapy of iron and copper overload is the use of low-molecular-weight chelators of these elements. However, these agents suffer from severe side effects, are often expensive and possess unfavorable pharmacokinetics, thus limiting the usability of such therapy. The emerging concepts are polymer-supported iron- and copper-chelating therapeutics, either for parenteral or oral use, which shows vivid potential to keep the therapeutic efficacy of low-molecular-weight agents, while avoiding their drawbacks, especially their side effects. Critical evaluation of this new perspective polymer approach is the purpose of this review article.

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“…After the classical MD simulations the 6G7/NLP Pya adduct was relaxed by 5 ps of QM (Born-Oppenheimer)/MM MD simulations performed with the CP2K 6.1 program [55] to properly describe the metal-ligand interactions [56]. The QM region comprised the sidechain atoms of Asp93 and Asp104 residues of NLP Pya , the 6G7 compound, the Mg 2+ ion and three water molecules (51 atoms), while the rest of the system (the protein and the explicit solvent) was treated at MM level with the same force field of the classical MD simulations.…”

Section: Qm/mm Molecular Dynamics Simulationsmentioning

confidence: 99%

Nep1-like proteins as a target for plant pathogen control

et al. 2021

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The lack of efficient methods to control the major diseases of crops most important to agriculture leads to huge economic losses and seriously threatens global food security. Many of the most important microbial plant pathogens, including bacteria, fungi, and oomycetes, secrete necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs), which critically contribute to the virulence and spread of the disease. NLPs are cytotoxic to eudicot plants, as they disturb the plant plasma membrane by binding to specific plant membrane sphingolipid receptors. Their pivotal role in plant infection and broad taxonomic distribution makes NLPs a promising target for the development of novel phytopharmaceutical compounds. To identify compounds that bind to NLPs from the oomycetes Pythium aphanidermatum and Phytophthora parasitica, a library of 587 small molecules, most of which are commercially unavailable, was screened by surface plasmon resonance. Importantly, compounds that exhibited the highest affinity to NLPs were also found to inhibit NLP-mediated necrosis in tobacco leaves and Phytophthora infestans growth on potato leaves. Saturation transfer difference-nuclear magnetic resonance and molecular modelling of the most promising compound, anthranilic acid derivative, confirmed stable binding to the NLP protein, which resulted in decreased necrotic activity and reduced ion leakage from tobacco leaves. We, therefore, confirmed that NLPs are an appealing target for the development of novel phytopharmaceutical agents and strategies, which aim to directly interfere with the function of these major microbial virulence factors. The compounds identified in this study represent lead structures for further optimization and antimicrobial product development.

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Frontiers of metal-coordinating drug design

Cited by 31 publications

References 158 publications

Integrated Multi-Omics Analysis Model to Identify Biomarkers Associated With Prognosis of Breast Cancer

Integrated Multi-Omics Analysis Model to Identify Biomarkers Associated With Prognosis of Breast Cancer

Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers

Nep1-like proteins as a target for plant pathogen control

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