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.
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.
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.
