Multifunctional diamine AGE/ALE inhibitors with potential therapeutical properties against Alzheimer's disease

Lohou, Elodie; Sasaki, Naoki; Boullier, Agnès; Sonnet, Pascal

doi:10.1016/j.ejmech.2016.04.069

Cited by 5 publications

(15 citation statements)

References 54 publications

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“…AGEs increase with aging and their formation has been related to the level of carbohydrates; so, they have been linked to diabetes and obesity [207], as well as other diseases including atherosclerosis, Alzheimer's disease, and renal insufficiency [208, 209]. Mass spectrometry-based techniques represent a key method in identifying protein adducts and the specific site of modification but their use is still limited in routine clinical analysis [210, 211].…”

Section: Markers Based On Ros-induced Modificationsmentioning

confidence: 99%

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Marrocco

Altieri

Peluso

2017

Oxidative Medicine and Cellular Longevity

618

500

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Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

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Section: Markers Based On Ros-induced Modificationsmentioning

confidence: 99%

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Marrocco

Altieri

Peluso

2017

Oxidative Medicine and Cellular Longevity

618

500

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“…As shown in Table 1 and Figure 1, our previously described synthetic strategy based on a key pseudopeptidic coupling step between diamine building blocks 2-6 and hydroxypyridinone (HOPO) ligands 9-10 was first extended to allow a decrease in size of the amide or piperazine-1,4-diamide linker and afforded the derivatives Ia-1 to Ia-4 or Ib-1 to Ib-3 respectively [8]. Moreover, simple alkyl chains could be introduced between the two functional moieties of 2-methyl-3,4-HOPO-diamine hybrids IIa-1 and IIa-2 carrying out a condensation of amino precursors 4 and 5 with maltol benzyl ether respectively.…”

Section: Chemical Synthesismentioning

confidence: 99%

“…As shown in Scheme 1 and according to previously described reaction conditions [8], a new azide precursor 2 was prepared starting from commercially available N-carboxybenzyl L-asparagine (N-Cbz-Asn-OH). The dehydration of its side-chain amide function using trifluoroacetic anhydride in pyridine first provided the cyano intermediate 11 in 92% yield.…”

Section: Synthesis Of New Diamine Building Blocks 2 5 7 Andmentioning

confidence: 99%

“…Diamine building blocks 3 and 4 have previously been synthesized by the transformation of respective α-carboxylic function of L-ornithine and L-lysine into the amine group [8]. Compound 4 was subjected to the oxidative deamination by sodium nitroprusside to give the corresponding hydroxyl intermediate 16 (Scheme 2) [14].…”

Section: Synthesis Of New Diamine Building Blocks 2 5 7 Andmentioning

confidence: 99%

“…With this AD-triggering biometal dyshomeostasis hypothesis in mind, we have previously reported the development of efficient AGE/ALE inhibitors as "multitarget-directed ligands" (MTDLs) [8,9]. These hydroxypyridinone-diamine hydrid molecules appear to be able to trap RCS (vicinal diamine function) as well as ROS and transition metals (hydroxypyridinone moiety) simultaneously.…”

Section: Introductionmentioning

confidence: 99%

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Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer’s Disease

et al. 2019

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There is an urgent need to propose effective treatments for Alzheimer’s disease (AD). Although the origin of the disease is poorly understood, several therapeutic options have been proposed. The new therapeutic approaches targeting biometal-mediated neurodegenerative pathways appear to be interesting ones. As a continuation of our preceding studies, two novel series of advanced glycation endproducts (AGE)/advanced lipid peroxidation endproducts (ALE) inhibitors have been developed as multifunctional scavengers. This extended work allowed us to highlight the new hydroxypyridinone-diamine hybrid IIa-3 bearing a C4 alkyl linker between the two pharmacophores. This derivative exhibited preserved potent capacities to trap reactive carbonyl species (vicinal diamine function) as well as reactive oxygen species and transition metals (hydroxypyridinone moiety) in comparison with previously described lead compound 1. In addition, its good predicted absorption, distribution, metabolism and excretion (ADME) properties were correlated with a better efficacy to inhibit in vitro methylglyoxal-induced apoptosis in neuronal-like PC12 cells. This new promising agent revealed improved druglikeness and ability to prevent biometal-mediated oxidative and carbonyl stress amplification involved in AD pathogenesis.

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3,2-Hydroxypyridinone-Grafted Chitosan Oligosaccharide Nanoparticles as Efficient Decorporation Agents for Simultaneous Removal of Uranium and Radiation-Induced Reactive Oxygen Species in Vivo

et al. 2018

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Most of the key radionuclides in the nuclear fuel cycle, such as actinides, possess a combination of heavy metal chemotoxicity and radiotoxicity and therefore represent a severe threat to the ecological environment and public safety. The radiotoxicity originates from direct radiation-induced organ damage and indirect damage, mostly through radiation-induced reactive oxygen species (ROS). Although effective chelating agents that can accelerate the excretion of actinides, such as uranium, have been developed in the past several decades, very few of them can reduce radiation-induced damage from internal contamination. In fact, the strategy of simultaneous removal of actinides and their induced-ROS in vivo has scarcely been considered. Here, we report a 3,2-hydroxypyridinone-grafted chitosan oligosaccharide nanoparticle (COS-HOPO) as a new type of decorporation agent that is effective for the removal of both uranium and ROS in vivo. The cytotoxicity and decorporation assays indicate that the marriage of chitosan oligosaccharide (COS) and hydroxypyridinone (HOPO) gives rise to a remarkable decrease in toxicity and promotion of the uranium removal capability from both kidneys and femurs. The decorporation efficacy can reach up to 43% in rat proximal tubular epithelial cells (NRK-52E), 44% in kidneys, and 32% in femurs. Moreover, the ROS levels of the cells treated with COS-HOPO are significantly lower than those of the control group, implying a promising radiation protection effect. The detoxification mechanism of COS-HOPO is closely related to both chelating U(VI)-and scavenging U(VI)-induced intracellular ROS.

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Multifunctional diamine AGE/ALE inhibitors with potential therapeutical properties against Alzheimer's disease

Cited by 5 publications

References 54 publications

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer’s Disease

3,2-Hydroxypyridinone-Grafted Chitosan Oligosaccharide Nanoparticles as Efficient Decorporation Agents for Simultaneous Removal of Uranium and Radiation-Induced Reactive Oxygen Species in Vivo

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