161392-59-2Relevant academic research and scientific papers
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.
Enantiospecific synthesis of (+)-ribasine
Ollero, Lourdes,Castedo, Luis,Dominguez, Domingo
, p. 4445 - 4456 (2007/10/03)
The alkaloid (+)-ribasine was synthesized by stereocontrolled addition of substituted α-lithium-o-toluate 6d to enantiomerically pure (R)-N-(9- phenylfluoren-9-yl)-2-amino-5,6-(methylenedioxy)indan-1-one [(+)-5]. Aminoindanone (+)-5 was prepared from amino acid (-)-15 obtained by diastereoselective alkylation of a chiral glyeme enolate synthon.
A New Convenient Route for the Synthesis of DOPA Peptides
Nakonieczna, Lucja,Przychodzen, Witold,Chimiak, Andrzej
, p. 1055 - 1058 (2007/10/02)
The tert-butyldimethylsilyl group as the catechol protective group of DOPA (compound 1a), Boc-DOPA (compound 1b) and DOPA esters (compounds 2a-c) is introduced.The compounds 2a-c and 1b are used as the starting substrates for the synthesis of the protecte
