61049-69-2Relevant academic research and scientific papers
Bifunctional 3-hydroxy-4-pyridinones as effective aluminium chelators: synthesis, solution equilibrium studies and in vivo evaluation
Irto, Anna,Cardiano, Paola,Chand, Karam,Cigala, Rosalia Maria,Crea, Francesco,De Stefano, Concetta,Gano, Lurdes,Sammartano, Silvio,Santos, Maria Amélia
, p. 116 - 129 (2018)
This paper reports the results on the study of a set of synthesized bifunctional 3-hydroxy-4-pyridinones chelators as potential aluminium sequestering agents. They were N-functionalized with alkyl-amino, -carboxylic and –(amino-carboxylic) groups, envisaging the improvement of the Al3+ sequestering capacity, in comparison with the marketed chelating drug deferiprone. The main focus of this work was given to the assessment of their binding ability towards Al3+, which was studied by potentiometric and UV–Vis spectrophotometric measurements carried out at T = 298.15 K. The speciation models were characterized by AlpLqHr (3p+r?qz) species with different stoichiometry. Depending on ligand side-chain structures and on their thermodynamic properties, different trends of stability was found. Furthermore, the sequestering ability of the ligands towards Al3+ was investigated by the calculation of pL0.5 values at different experimental conditions. These results clearly indicate that the presence of amino-carboxylic groups in the ligands increases the sequestering ability towards Al3+. The in silico evaluation of pharmacokinetic descriptors indicated no violation to the Lipinski's rule and drug-likeness properties. Furthermore, the in vivo bioassays on a model of metal-overload mice showed for three investigated ligands a higher metal-sequestering capacity than for the chelating drug deferiprone, thus suggesting their potential interest as Al-chelating drug candidates.
DIBI, a 3-hydroxypyridin-4-one chelator iron-binding polymer with enhanced antimicrobial activity
Ang, M. Trisha C.,Gumbau-Brisa, Roger,Allan, David S.,McDonald, Robert,Ferguson, Michael J.,Holbein, Bruce E.,Bierenstiel, Matthias
, p. 1206 - 1212 (2018)
Depriving microorganisms of bioavailable iron is a promising strategy for new anti-infective agents. The new, highly water-soluble, low molecular weight co-polymer DIBI was developed to selectively bind iron(iii) ions as a tris chelate and acts as a standalone anti-infective. Minimum inhibitory concentration (MIC) studies show DIBI is effective against representative reference strains for Gram-positive and Gram-negative bacteria S. aureus and A. baumannii, and the fungus C. albicans. Compared to the small molecule iron chelators, deferiprone and deferoxamine, DIBI outclassed these by factors of 100 to 1000 for inhibition of initial growth. DIBI and a series of related co-polymers (Mw of 2-9 kDa) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization of a chelating 3-hydroxypyridin-4-one (HPO) methacrylamide monomer and N-vinylpyrrolidone (NVP). Full incorporation of the HPO monomer into the co-polymers from the reaction solution was determined by 1H NMR spectroscopy and ranged from 4.6 to 25.6 mol%. UV-vis spectroscopy showed that all the HPO in DIBI binds readily to iron(iii) in a tris chelate mode to the maximum theoretical iron(iii) binding capacity of the co-polymer. Chemical characterization including single crystal X-ray diffraction analyses of the O-benzyl protected and the functional HPO monomer are discussed. By design, DIBI is highly water soluble; the highest mass fraction in water tested was 70% w/w, without the need of organic co-solvents.
New polyazamacrocyclic 3-hydroxy-4-pyridinone based ligands for iron depletion antitumor activity
Dong, Xiuxiu,He, Chuanchuan,Liu, Xiaoguang,Ma, Xiang,Xiang, Guangya,Zhang, Xiaojuan
, (2020)
Iron depletion is an efficient strategy for the development of anticancer agents. In an effort to develop efficient chelators, two new 3-hydroxy-4-pyridinone based polyazamacrocycles 1e and 2e were designed and synthesized. A preliminary study of the liga
In silico to in vitro screening of hydroxypyridinones as acetylcholinesterase inhibitors
Telpoukhovskaia, Maria A.,Patrick, Brian O.,Rodríguez-Rodríguez, Cristina,Orvig, Chris
, p. 1624 - 1628 (2016)
We have previously shown the improved acetylcholinesterase inhibitory activity of a model hydroxypyridinone compound transforming the hydroxyl group on the main ring into an N,N-dimethylcarbamate group; in the course of that study we developed a computational model to screen compounds for enzymatic activity. Herein we report development of second generation libraries. Candidates that adhere to drug-like criteria from a virtual library of compounds were tested using computational docking studies. Synthesis and characterization of chosen test compounds and their acetylcholinesterase inhibitory activity are presented.
Phenylethylene glycol-derived LpxC inhibitors with diverse Zn2+-binding groups
Galster, Magdalena,L?ppenberg, Marius,Galla, Fabian,B?rgel, Frederik,Agoglitta, Oriana,Kirchmair, Johannes,Holl, Ralph
, p. 486 - 509 (2019)
The Zn2+-dependent bacterial deacetylase LpxC is a promising target for the development of novel antibiotics. Most of the known LpxC inhibitors carry a hydroxamate moiety as Zn2+-binding group. However, hydroxamic acids generally exh
Preparation method of intermediate of antiviral drug
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Paragraph 0061-0064, (2021/06/22)
The invention relates to a preparation method of an intermediate of an antiviral drug, belonging to the field of medicinal chemistry. According to the method provided by the invention, raw materials react with an alkene forming reagent under the condition that Lewis acid and acid anhydride are added to prepare an intermediate compound; and then the intermediate compound reacts under the action of sodium periodate, and then post-treatment is conducted under the conditions of alkali and an oxidizing agent to obtain the intermediate. According to the method disclosed by the invention, reagents with relatively high toxicity or relatively high price and conditions such as extremely low temperature which is difficult to reach or control are not needed, used reagents are cheap and easy to obtain, reaction conditions are easy to control and implement, and the method has relatively high industrial application value.
Polycyclic pyridine oxime-based compound as well as pharmaceutical composition and application thereof
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Paragraph 0150-0153, (2021/11/26)
The invention discloses a polycyclic pyridine oxime-based compound and a pharmaceutical composition and application thereof, wherein the polycyclic pyridine oxime-based compound is shown as a formula (I). The compound shows strong inhibition of influenza
Design, synthesis and biological evaluation of potential anti-AD hybrids with monoamine oxidase B inhibitory and iron-chelating effects
Guo, Jianan,Mi, Zhisheng,Jiang, Xiaoying,Zhang, Changjun,Guo, Zili,Li, Linzi,Gu, Jinping,Zhou, Tao,Bai, Renren,Xie, Yuanyuan
, (2020/12/29)
A series of active hybrids combining 3-hydroxypyridin-4(1H)-one and coumarin pharmacophores were designed and synthesized as potential agents for the treatment of Alzheimer's disease (AD). All the compounds exhibited excellent iron-chelating activities (p
Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans
Bortolami, Martina,Pandolfi, Fabiana,Messore, Antonella,Rocco, Daniele,Feroci, Marta,Di Santo, Roberto,De Vita, Daniela,Costi, Roberta,Cascarino, Paola,Simonetti, Giovanna,Scipione, Luigi
, (2021/05/13)
Candida albicans, in specific conditions, is responsible of severe invasive systemic candidiasis that are related to its ability to produce biofilm on biological and artificial surfaces. Many studies reported the role of iron in fungal growth and virulence and the ability of metal chelating agents to interfere with C. albicans metabolism, virulence and biofilm formation. Here we report the activity of 3-hydroxy-1,2-dimethyl-4(1H)-pyridinone (deferiprone) derivatives against C. albicans planktonic cells and biofilm. Some of the studied compounds (2b and 3b) were able to chelate Fe(III) and Cu(II), and showed an interesting activity on planktonic cells (MIC50 of 32 μg/mL and 16 μg/mL respectively) and on biofilm formation (BMIC50 of 32 μg/mL and 16 μg/mL respectively) in cultured ATCC 10,231C. albicans; this activity was reduced, in a concentration dependent way, by the addition of Fe(III) and Cu(II) to the culture media. Furthermore, the most active compound 3b showed a low toxicity on Galleria mellonella larvae.
Design and synthesis of N-hydroxyalkyl substituted deferiprone: a kind of iron chelating agents for Parkinson's disease chelation therapy strategy
Zhang, Qingchun,Feng, Shufan,Zhao, Yulian,Jin, Bo,Peng, Rufang
, p. 467 - 478 (2021/05/13)
The blood–brain barrier (BBB) permeability of molecules needs to meet stringent requirements of Lipinski’s rule, which pose a difficulty for the rational design of efficient chelating agents for Parkinson's disease chelation therapy. Therefore, the iron c
