7101-51-1Relevant articles and documents
Structural Transformative Antioxidants for Dual-Responsive Anti-Inflammatory Delivery and Photoacoustic Inflammation Imaging
Zhao, Caiyan,Chen, Jingxiao,Ye, Jiamin,Li, Zhi,Su, Lichao,Wang, Junqing,Zhang, Ye,Chen, Jinghua,Yang, Huanghao,Shi, Jinjun,Song, Jibin
supporting information, p. 14458 - 14466 (2021/05/13)
We have synthesized a PEGylated, phenylboronic acid modified L-DOPA pro-antioxidant (pPAD) that can self-assemble into nanoparticles (pPADN) for the loading of a model glucocorticoid dexamethasone (Dex) through 1,3-diol/phenylboronic acid chemistry and hydrophobic interactions for more effective treatment of inflammation. Upon exposure to ROS, pPADN convert into the active form of L-DOPA, and a cascade of oxidative reactions transform it into antioxidative melanin-like materials. Concomitantly, the structural transformation of pPADN triggers the specific release of Dex, along with the acidic pH of inflammatory tissue. In a rat model of osteoarthritis, Dex-loaded pPADN markedly mitigate synovial inflammation, suppress joint destruction and cartilage matrix degradation, with negligible in vivo toxicity. Moreover, in situ structural transformation makes pPADN suitable for noninvasive monitoring of therapeutic effects as a photoacoustic imaging contrast agent.
Easy access to drug building-blocks through benzylic C-H functionalization of phenolic ethers by photoredox catalysis
Brandhofer, Tobias,Derdau, Volker,García Manche?o, Olga,Méndez, María,P?verlein, Christoph,Stinglhamer, Martin
supporting information, p. 6756 - 6759 (2021/07/13)
A visible light-mediated photocatalyzed C-C-bond forming method for the benzylic C-H functionalization of phenolether containing synthetic building blocks based on a radical-cation/deprotonation strategy is reported. This method allows the mild, selective generation of benzyl radicals in phenolic complex molecules and drug-like compounds, providing new entries in synthetic and medicinal chemistry.
Small Molecule Inhibits Metal-Dependent and -Independent Multifaceted Toxicity of Alzheimer's Disease
Samanta, Sourav,Rajasekhar, Kolla,Babagond, Vardhaman,Govindaraju, Thimmaiah
, p. 3611 - 3621 (2019/09/10)
Alzheimer's disease (AD) is one of the most devastating forms of dementia, without reliable treatments to cure, delay the onset, or prevent the disease progression. The proposed toxic mechanisms of AD include amyloidogenesis of amyloid β (Aβ), metal ion dyshomeostasis, redox active metal-Aβ inclusion complex formation, and generation of excessive reactive oxygen and nitrogen species (ROS and RNS). The imbalance in redox homeostasis causes oxidative stress, DNA damage, mitochondrial dysfunction, and inflammation, which collectively become a major hurdle in the development of effective therapeutic agents for multifactorial AD. This necessitates a multifunctional strategy to develop effective therapeutic agents to inhibit multifaceted toxicity. In this context, we report a rational design, synthesis, and detailed study to identify a small molecule multifunctional modulator (MFM) inspired by the human origin tripeptide. The lead, MFM 4, chelates and sequesters metal ions, disrupts their redox cycles, prevents excessive ROS production and oxidative stress, ameliorates oxidative DNA damage and mitochondrial dysfunction, and modulates Nrf2 protein signaling under oxidative stress conditions by eliminating the toxic stress elements. The MFM 4 was found to inhibit metal-dependent and -independent Aβ aggregation and qualified as a suitable candidate to inhibit Aβ-induced neuronal toxicity. The NMR spectroscopy study revealed molecular-level interactions of 4 with Aβ42, which explain the mechanism of aggregation inhibition. Furthermore, 4 effectively inhibited inflammation as revealed by reduction in nitric oxide (NO) production in LPS-activated glial cells. These key features make 4 a potential MFM platform to develop therapeutic agents for metal (Cu, Zn and Fe)-dependent and -independent multifaceted Aβ toxicity of AD.
Water-soluble L-DOPA esters
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Paragraph 0082, (2018/05/24)
The present invention relates to novel compounds of the formula I, methods for their preparation and their use for treatment of diseases. The invention discloses the synthesis of levodopa (L-DOPA) esters by coupling polyhydroxy compounds or their derivatives to the L-DOPA carboxyl group. The synthesis allows to produce L-DOPA derivatives which are highly soluble in water as well as aqueous and biocompatible liquids and have an improved hydrolytic stability in water or aqueous and biocompatible media for an application over several days. The invention helps producing L-DOPA substances for applications in the fields of medicine, biology and medical engineering as well as in the pharmaceutical industry.
Base/Cryptand/Metal-Free Automated Nucleophilic Radiofluorination of [18F]FDOPA from Iodonium Salts: Importance of Hydrogen Carbonate Counterion
Maisonial-Besset, Aurélie,Serre, Audrey,Ouadi, Ali,Schmitt, Sébastien,Canitrot, Damien,Léal, Fernand,Miot-Noirault, Elisabeth,Brasse, David,Marchand, Patrice,Chezal, Jean-Michel
supporting information, p. 7058 - 7065 (2019/01/04)
As evidenced by the number of publications and patents published in the last years, the radiosynthesis of 6-[18F]fluoro-3,4-dihydroxy-L-phenylalanine ([18F]FDOPA) using the nucleophilic [18F]F- process remains currently a challenge for the radiochemists scientific community even if promising methods for the radiofluorination of electron-rich aromatic structures were recently developed from arylboronate, arylstannane or iodonium salt precursors. In such context, based on the use of an iodonium triflate salt precursor, we optimized a fast and efficient radiofluorination route fully automated and free from any base, cryptand or metal catalyst for the radiosynthesis of [18F]FDOPA. Using this method, this clinically relevant radiotracer was produced in 64 min, 27–38 % RCY d.c. (n = 5), >99 % RCP, >99 % ee., and high Am 170–230 GBq/μmol. In addition, this optimization study clearly highlighted the important role of a triflate-hydrogen carbonate counterion exchange during the radiolabeling process to achieve high fluorine-18 incorporation yields.
A self-assembled tetrapeptide that acts as a “turn-on” fluorescent sensor for Hg2+ ion
Tomar, Kalpana,Kaur, Gagandeep,Verma, Sandeep,Ramanathan, Gurunath
supporting information, p. 3653 - 3656 (2018/09/11)
The tetrapeptide (Bz-ΔPhe(p-NPh2)-L-DOPA(protected)-L-Phe-L-Phe-OMe was designed to incorporate seven phenyl rings so that it's conformation, self-assembly and application in Hg2+ ions sensing could be studied. Peptide molecules adopted an overlapping β-turn of type III/III conformation in crystals. The peptide showed a highly selective turn-on response towards mercuric ion over other metal ions with a 10-fold enhancement in fluorescence intensity. This intensity change coupled with the selectivity of the peptide towards mercury allowed us to demonstrate simple colorimetric dip sensing of Hg2+ ions. The technique provides a highly selective and effective way to detect Hg2+ ions. The peptide also self-assembled into nanospheres with diameter ranges from 100 to 500 nm. Mercuric ion coordination enabled these peptide nanospheres to aggregate into well-defined nanoparticles. The enhanced fluorescence upon Hg2+ addition demonstrates that peptide scaffolds can be exploited in the development of different selective sensors.
Synthesis and cytotoxicity of dinuclear platinum(II) complexes of (1S, 3S)-1,2,3,4-tetrahydroisoquinolines
Xu, Geng,Guo, Ju,Yan, Zheng,Wang, Nan,Liu, Zhan-Zhu
, p. 186 - 188 (2013/06/26)
A series of novel dinuclear platinum(II) complexes with (1S, 3S)-1,2,3,4-tetrahydroisoquinolines as the ligands were synthesized as potential anticancer agents in several steps starting from commercially available l-DOPA. The cytotoxicities of the series of dinuclear platinum(II) complexes of tetrahydroisoquinoline were tested against HCT-8, BEL-7402, A2780, MCF-7, Hela, A549 and BGC-823 cell lines by the MTT test. These complexes showed selective inhibition activity against cisplatin-insensitive cell line Skov3.
Total synthesis of pyoverdin D
Mashiach, Roi,Meijler, Michael M.
supporting information, p. 1702 - 1705 (2013/06/27)
Pyoverdin D is an important siderophore that is used by the human pathogen Pseudomonas aeruginosa to import iron and gain a competitive advantage. This unique partially cyclic octapeptide bears four nonproteinogenic amino acids, including δN-formyl-δN-hydroxy-l-ornithine, and a catechol containing chiral chromophore. Here, we report the first total synthesis of pyoverdin D.
Synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via a Pictet-Spengler approach
Larsson, Rikard,Blanco, Narda,Johansson, Martin,Sterner, Olov
supporting information, p. 4966 - 4970 (2012/11/07)
A protocol for the diastereoselective synthesis of C-1 indol-3-yl substituted tetrahydroisoquinoline derivatives via Pictet-Spengler condensation with L-DOPA or l-DOPA derivatives and 1H-indole-3-carbaldehydes is presented. The protocol is used for the successful synthesis of several tetrahydroisoquinolines as well as diketopiperazine fused analogues.
An Au(I)-catalysed allenamide cyclisation giving access to an α-vinyl-substituted tetrahydroisoquinoline building block
Singh, Sanjitpal,Elsegood, Mark R. J.,Kimber, Marc C.
scheme or table, p. 565 - 568 (2012/04/04)
An Au(I)-catalysed intramolecular hydroarylation of an enantiopure allenamide has been achieved and has given access to a key α-vinyl- substititued tetrahydroisoquinoline. Additionally this has been accomplished in very high yield and high diastereoselectivity. Georg Thieme Verlag Stuttgart · New York.
