22492-19-9Relevant articles and documents
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Pozharskii,A.F. et al.
, (1969)
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Novel multi-target compounds in the quest for new chemotherapies against Alzheimer's disease: An experimental and theoretical study
Martínez, Alberto,Zahran, Mai,Gomez, Miguel,Cooper, Coreen,Guevara, Johnny,Ekengard, Erik,Nordlander, Ebbe,Alcendor, Ralph,Hambleton, Sarah
, p. 4823 - 4840 (2018/09/11)
The lack of any effective therapy along with the aging world population anticipates a growth of the worldwide incidence of Alzheimer's disease (AD) to more than 100 million cases by 2050. Accumulation of extracellular amyloid-β (Aβ) plaques, intracellular tangles in the brain, and formation of reactive oxygen species (ROS) are the major hallmarks of the disease. In the amyloidogenic process, a β-secretase, known as BACE 1, plays a fundamental role in the production of Aβ fragments, and therefore, inhibition of such enzymes represents a major strategy for the rational design of anti-AD drugs. In this work, a series of four multi-target compounds (1–4), inspired by previously described ionophoric polyphenols, have been synthesized and studied. These compounds have been designed to target important aspects of AD, including BACE 1 enzymatic activity, Aβ aggregation, toxic concentrations of Cu2+ metal ions and/or ROS production. Two other compounds (5 and 6), previously reported by some of us as antimalarial agents, have also been studied because of their potential as multi-target species against AD. Interestingly, compounds 3 and 5 showed moderate to good ability to inhibit BACE 1 enzymatic activity in a FRET assay, with IC50′s in the low micromolar range (4.4 ± 0.3 and 1.7 ± 0.3 μM, respectively), comparable to other multi-target species, and showing that the observed activity was in part due to a competitive binding of the compounds at the active site of the enzyme. Theoretical docking calculations overall agreed with FRET assay results, displaying the strongest binding affinities for 3 and 5 at the active site of the enzyme. In addition, all compounds selectively interacted with Cu2+ metal ions forming 2:1 complexes, inhibited the production of Aβ-Cu2+ catalyzed hydroxyl radicals up to a ～100% extent, and scavenged AAPH-induced peroxyl radical species comparably to resveratrol, a compound used as reference in this work. Our results also show good anti-amyloidogenic ability: compounds 1–6 inhibited both the Cu2+-induced and self-induced Aβ(1–40) fibril aggregation to an extent that ranged from 31% to 77%, while they disaggregated pre-formed Aβ(1–40) mature fibrils up to a 37% and a 69% extent in absence and presence of Cu2+, respectively. Cytotoxicity was additionally studied in Tetrahymena thermophila and HEK293 cells, and compared to that of resveratrol, showing that compounds 1–6 display lower toxicity than that of resveratrol, a well-known non-toxic polyphenol.
Iron Nanoparticles Embedded in Graphitic Carbon Matrix as Heterogeneous Catalysts for the Oxidative C?N Coupling of Aromatic N?H Compounds and Amides
He, Jinbao,Dhakshinamoorthy, Amarajothi,Primo, Ana,Garcia, Hermenegildo
, p. 3003 - 3012 (2017/08/15)
Fe or Co nanoparticles (NPs) and two nanoparticulate Fe-Co alloys having different Fe/Co atomic ratio with average particle size ranging from 10.9 to 26.5 nm embedded in turbostratic graphitic carbon matrix have been prepared by pyrolysis at 900 °C under
